Amyloid Neuropathies
Amyloid Neuropathies, Familial
Prealbumin
Amyloidosis
Amyloid
Diabetic Neuropathies
Amyloid beta-Peptides
Serum Amyloid A Protein
Peripheral Nervous System Diseases
Amyloid beta-Protein Precursor
Hereditary Sensory and Motor Neuropathy
Islet Amyloid Polypeptide
Cerebral Amyloid Angiopathy
Hereditary Sensory and Autonomic Neuropathies
Optic Neuropathy, Ischemic
Serum Amyloid P-Component
Polyneuropathies
Sural Nerve
Amyloid Precursor Protein Secretases
Alzheimer Disease
Capture of a dimeric intermediate during transthyretin amyloid formation. (1/93)
Point mutations in the human plasma protein transthyretin are associated with the neurological disorder familial amyloidosis with polyneuropathy type 1. The disease is characterized by amyloid fibril deposits causing damage at the site of deposition. Substitution of two amino acids in the hydrophobic core of transthyretin lead to a mutant that was very prone to form amyloid. In addition, this mutant has also been shown to induce a toxic response on a neuroblastoma cell line. Renaturation of the transthyretin mutant at low temperature facilitated the isolation of an amyloid-forming intermediate state having the apparent size of a dimer. Increasing the temperature effectively enhanced the rate of interconversion from a partly denatured protein to mature amyloid. Using circular dichroism the beta-sheet content of the formed mature fibrils was significantly lower than that of the native fold of transthyretin. Morphology studies using electron microscopy also indicated a temperature-dependent transformation from amorphous aggregates toward mature amyloid fibrils. In addition, 1-anilino-8-naphtalenesulfonate fluorescence studies suggested the loss of the thyroxin-binding channel within both the isolated intermediate and the mature fibrils. (+info)Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. (2/93)
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. No systematic immunohistochemical data exists relating TTR deposition with FAP progression. We assessed nerves from FAP patients in different stages of disease progression (FAP 0 to FAP 3) for TTR deposition by immunohistochemistry, and for the presence of amyloid fibrils by Congo Red staining. The nature of the deposited material was further studied by electron microscopy. We observed that early in FAP (FAP 0), TTR is already deposited in an aggregated nonfibrillar form, negative by Congo Red staining. This suggested that in vivo, preamyloidogenic forms of TTR exist in the nerve, in a stage before fibril formation. Cytotoxicity of nonfibrillar TTR was assessed in nerves of different FAP stages by immunohistochemistry for macrophage colony-stimulating factor. FAP 0 patients already presented increased axonal expression of macrophage colony-stimulating factor that was maintained in all other stages, in sites related to TTR deposition. Toxicity of synthetic TTR fibrils formed in vitro at physiological pH was studied on a Schwannoma cell line by caspase-3 activation assays and showed that early aggregates but not mature fibrils are toxic to cells. Taken together, these results show that nonfibrillar cytotoxic deposits occur in early stages of FAP. (+info)Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy. (3/93)
BACKGROUND: Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS: Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS: Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines. (+info)Results of liver transplantation for familial amyloid polyneuropathy type I in Brazil. (4/93)
Familial amyloid polyneuropathy type I (FAP-I) is an inherited amyloidosis secondary to systemic deposition of amyloid fibrils containing mutant transthyretin (TTR) variants. The disease has a progressive clinical course and is usually fatal 10 years after its onset. TTR is mainly produced in hepatocytes, and liver transplantation (LT) has been proposed as an effective treatment for FAP-I. The aim of this study is to evaluate the results of LT for FAP-I in Brazil and analyze prognostic factors associated with survival after surgery. Twenty-four patients (median age, 36 years; range, 25 to 52 years) who underwent LT with the diagnosis of FAP-I were evaluated. Surgery was uneventful in all but six patients who died of complications of primary liver nonfunction (n = 1), cardiogenic shock (n = 1), sepsis (n = 3), and hepatic artery thrombosis (n = 3). Overall 1- and 5-year survival rates were 70% and 58%, respectively. Most patients had stabilization or improvement of symptoms after a median follow-up of 36 months (range, 14 to 82 months). Survivors had a shorter disease duration before LT (median, 6 years; range, 2 to 17 years v 9 years; range, 7 to 12 years; P =.02), greater albumin levels (median, 4 g/dL; range, 3 to 4.7 g/dL v 3.6 g/dL; range, 2.6 to 4.1 g/dL; P =.03), and greater modified body mass index scores (median, 735; range, 502 to 1,432 v 659; range, 411 to 803; P =.04) compared with nonsurvivors. However, only disease duration and albumin levels were independently associated with survival in multivariate analysis. In conclusion, LT is an effective therapy for FAP-I. Mortality after surgery is associated with poor nutritional status and long-standing disease before LT. Thus, LT should be performed as early as possible after the onset of FAP-I symptoms to avoid major disability and improve survival. (+info)Long-term follow-up of survival of liver transplant recipients with familial amyloid polyneuropathy (Portuguese type). (5/93)
Portuguese type familial amyloid polyneuropathy is a dominantly inherited neuropathic amyloidosis caused by a mutant transthyretin (TTR). Because TTR is produced mainly by the liver, liver transplantation (LT) abolishes production of the amyloidogenic variant TTR. To date, the procedure appears to halt the progress of the disease. However, long-term outcome is unknown. The aim of the present study is to evaluate the survival of our initial group of unselected liver transplant recipients with FAP. Seventy patients, 51 transplant recipients and a control group of 19 nontransplantation patients, with disease onset before the age of 55 years were included on the study. Transplant recipients were divided into two categories: (1) early series, with patients followed up for 5 years or longer, and (2) new series, with patients followed up for 1 to 5 years. Nonparametric statistical methods were used. Binary regression analyses were performed by stepwise logistic regression and Cox proportional hazard regression. Survival analysis was performed using Kaplan-Meier analysis, the Cox-Mantel test. Survival analyses and Cox proportional hazard regression analysis were performed from disease onset, not from LT. Significantly decreased survival was noted for transplant recipients with a modified body mass index (mBMI) less than 600 compared with the control group (P < .05). A significant difference in survival also was observed between transplant recipients with an mBMI greater than 600 at the time of LT compared with those with an mBMI less than 600 (P < .02). mBMI and age at LT had a significant impact on survival; whereas late deaths were related to age at LT, early deaths were related to mBMI. The cumulative 10-year survival rate after disease onset was 94% in the new series, with one early death (< 6 months) after LT, compared with a 78% survival rate and eight early deaths in the early series (P = .1). (+info)Effect of the intestinal flora on amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy. (6/93)
Familial amyloidotic polyneuropathy (FAP) is a hereditary disease characterized by the systemic accumulation of amyloid fibrils. A mutant transthyretin (TTR) gene is mainly responsible for the disease. However, the variable age of onset and low penetrance might be due to environmental factors, one of which is the intestinal flora. Three types of intestinal flora were introduced into a transgenic (Tg) mouse FAP model, 6.0-hMet30. The CV1 and CV2 group transgenic mice were transferred with the intestinal flora from two different mouse facilities housed under conventional conditions, and the SPF group transgenic mice were kept under specific pathogen free conditions in our facility. All the mice were maintained under controlled temperature, humidity and bacterial conditions. Over a period of 28 months, amyloid was not deposited in the SPF and CV1 groups. In contrast, amyloid was deposited in the esophagus and small intestine of two of the three CV2 mice at 18 months. Many neutrophils infiltrated the lesions. The numbers of tissue neutrophils were higher in the CV2 group than in the SPF and CV1 groups at 18 months. The CV2 flora included fewer gram-positive anaerobic cocci as well as higher proportions of yeasts, staphylococci and enterobacteriaceae compared with the SPF and CV1 flora. These findings suggest that the intestinal flora plays an important role in amyloid deposition. (+info)Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. (7/93)
Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant disorder characterized by systemic extracellular deposition of transthyretin (TTR) amyloid fibrils. Several groups have generated transgenic mice carrying human TTR Val30Met, the most common mutation in FAP. To study amyloidogenicity and cytotoxicity of different TTRs, we produced transgenic mice expressing human TTR Leu55Pro, one of the most aggressive FAP-related mutations. TTR deposition and presence of amyloid fibrils was investigated and compared to animals carrying the human TTR Val30Met gene kept under the same conditions. Deposition in a C57BL/6J background (TTR-Leu55Pro mice) and in a TTR-null background [TTR-Leu55Pro X TTR-knockout (KO) mice] was compared. Animals in a C57BL/6J background presented early (1 to 3 months) nonfibrillar TTR deposition but amyloid was absent. In a TTR-null background, presence of amyloid fibrils was detected starting at 4 to 8 months with a particular involvement of the gastrointestinal tract and skin. This data suggested that TTR homotetramers are more prone to fibril formation than TTR murine wild-type/human mutant heterotetramers. The nature of the deposited material was further investigated by immunocytochemistry. Both amorphous aggregates and small TTR fibrils were present in TTR-Leu55Pro X TTR-KO transgenics. We observed that these TTR deposits mimic the toxic effect of TTR deposits in FAP: animals with TTR deposition, present approximately twofold increased levels of nitrotyrosine in sites related to deposition. The TTR-Leu55Pro X TTR-KO mice here described are an important tool for the dual purpose of investigating factors involved in amyloidogenesis and in cytotoxicity of deposited TTR. (+info)Familial ATTR amyloidosis: microalbuminuria as a predictor of symptomatic disease and clinical nephropathy. (8/93)
BACKGROUND: Portuguese type familial amyloid polyneuropathy (FAP) is a neuropathic amyloidosis caused by a mutant transthyretin (TTR). Varying degrees of renal involvement have been reported. Our aim was to assess the value of microalbuminuria (MA) for predicting clinical neurological disease and overt nephropathy in TTR-related amyloidosis. METHODS: All subjects had the TTR Val30Met mutation, and were recruited between 1993 and 1999. We have prospectively evaluated 22 asymptomatic gene carriers (7 male, 15 female; mean age 41.6+/-9.6 years) and 32 patients with neuropathy (14 male, 18 female; 36.8+/-8.8 years, on average, 33.0+/-9.3 years at the onset of neuropathy). We measured urinary albumin excretion every year, if asymptomatic, or every 6 months if already affected. Kidney biopsies were performed in patients with normal urinary albumin excretion, MA, and overt nephropathy, respectively. RESULTS: In asymptomatic carriers, persistent MA was detected in eight (36%) subjects. The presence of MA in asymptomatic gene carriers, compared with those having normal urinary albumin excretion, conferred a 4.8-fold risk of developing neuropathy, usually within the subsequent 3 years. Once neurological signs appeared, nephropathy, manifested as MA, progressed to overt nephropathy in one-half of subjects. In patients with neuropathy, 24 (75%) had MA during follow-up: evolution towards clinical renal disease occurred in 14 (58%) and renal failure occurred in five (21%), always after a course of MA. Proteinuria or renal failure without prior persistent MA were never observed in the present patient cohort. Histopathological evaluation did not reveal glomerular lesions other than amyloid deposits to explain abnormal urinary albumin excretion. The amount of mesangial and vascular-pole amyloid deposits was correlated with the degree of albuminuria. CONCLUSIONS: Microalbuminuria represents the first stage of clinical TTR amyloid nephropathy and is premonitory of neuropathy. Its presence identifies a subgroup of patients who are more prone to develop overt nephropathy. Screening of MA may be important to assess disease onset and to recommend liver transplantation in individuals at risk. (+info)Amyloid neuropathies are a group of peripheral nerve disorders caused by the abnormal accumulation of amyloid proteins in the nerves. Amyloid is a protein that can be produced in various diseases and can deposit in different organs, including nerves. When this occurs in the nerves, it can lead to damage and dysfunction, resulting in symptoms such as numbness, tingling, pain, and weakness in the affected limbs.
There are several types of amyloid neuropathies, with the two most common being:
1. Transthyretin (TTR)-related hereditary amyloidosis: This is an inherited disorder caused by mutations in the TTR gene, which leads to the production of abnormal TTR protein that can form amyloid deposits in various organs, including nerves.
2. Immunoglobulin light chain (AL) amyloidosis: This is a disorder in which abnormal plasma cells produce excessive amounts of immunoglobulin light chains, which can form amyloid deposits in various organs, including nerves.
The diagnosis of amyloid neuropathies typically involves a combination of clinical evaluation, nerve conduction studies, and tissue biopsy to confirm the presence of amyloid deposits. Treatment options depend on the underlying cause of the disorder and may include medications, chemotherapy, stem cell transplantation, or supportive care to manage symptoms.
Familial amyloid neuropathies are a group of inherited disorders characterized by the accumulation of abnormal deposits of amyloid proteins in various tissues and organs of the body. These abnormal deposits can cause damage to nerves, leading to a peripheral neuropathy that affects sensation, movement, and organ function.
There are several types of familial amyloid neuropathies, each caused by different genetic mutations. The most common type is known as transthyretin-related hereditary amyloidosis (TTR-HA), which is caused by mutations in the TTR gene. Other types include apolipoprotein A1-related hereditary amyloidosis (APOA1-HA) and gelsolin-related amyloidosis (AGel-HA).
Symptoms of familial amyloid neuropathies can vary depending on the type and severity of the disorder. Common symptoms include:
* Numbness, tingling, or pain in the hands and feet
* Weakness or loss of muscle strength in the legs and arms
* Autonomic nervous system dysfunction, leading to problems with digestion, heart rate, blood pressure, and temperature regulation
* Carpal tunnel syndrome
* Eye abnormalities, such as vitreous opacities or retinal deposits
* Kidney disease
Familial amyloid neuropathies are typically inherited in an autosomal dominant manner, meaning that a child has a 50% chance of inheriting the mutated gene from an affected parent. Diagnosis is usually made through genetic testing and confirmation of the presence of amyloid deposits in tissue samples.
Treatment for familial amyloid neuropathies typically involves managing symptoms and slowing the progression of the disease. This may include medications to control pain, physical therapy to maintain muscle strength and mobility, and devices such as braces or wheelchairs to assist with mobility. In some cases, liver transplantation may be recommended to remove the source of the mutated transthyretin protein.
Prealbumin, also known as transthyretin, is a protein produced primarily in the liver and circulates in the blood. It plays a role in transporting thyroid hormones and vitamin A throughout the body. Prealbumin levels are often used as an indicator of nutritional status and liver function. Low prealbumin levels may suggest malnutrition or inflammation, while increased levels can be seen in certain conditions like hyperthyroidism. It is important to note that prealbumin levels should be interpreted in conjunction with other clinical findings and laboratory tests for a more accurate assessment of a patient's health status.
Amyloidosis is a medical condition characterized by the abnormal accumulation of insoluble proteins called amyloid in various tissues and organs throughout the body. These misfolded protein deposits can disrupt the normal function of affected organs, leading to a range of symptoms depending on the location and extent of the amyloid deposition.
There are different types of amyloidosis, classified based on the specific proteins involved:
1. Primary (AL) Amyloidosis: This is the most common form, accounting for around 80% of cases. It results from the overproduction and misfolding of immunoglobulin light chains, typically by clonal plasma cells in the bone marrow. The amyloid deposits can affect various organs, including the heart, kidneys, liver, and nervous system.
2. Secondary (AA) Amyloidosis: This form is associated with chronic inflammatory diseases, such as rheumatoid arthritis, tuberculosis, or familial Mediterranean fever. The amyloid fibrils are composed of serum amyloid A protein (SAA), an acute-phase reactant produced during the inflammatory response. The kidneys are commonly affected in this type of amyloidosis.
3. Hereditary or Familial Amyloidosis: These forms are caused by genetic mutations that result in the production of abnormal proteins prone to misfolding and amyloid formation. Examples include transthyretin (TTR) amyloidosis, fibrinogen amyloidosis, and apolipoprotein AI amyloidosis. These forms can affect various organs, including the heart, nerves, and kidneys.
4. Dialysis-Related Amyloidosis: This form is seen in patients undergoing long-term dialysis for chronic kidney disease. The amyloid fibrils are composed of beta-2 microglobulin, a protein that accumulates due to impaired clearance during dialysis. The joints and bones are commonly affected in this type of amyloidosis.
The diagnosis of amyloidosis typically involves a combination of clinical evaluation, imaging studies, and tissue biopsy with the demonstration of amyloid deposition using special stains (e.g., Congo red). Treatment depends on the specific type and extent of organ involvement and may include supportive care, medications to target the underlying cause (e.g., chemotherapy, immunomodulatory agents), and organ transplantation in some cases.
Amyloid is a term used in medicine to describe abnormally folded protein deposits that can accumulate in various tissues and organs of the body. These misfolded proteins can form aggregates known as amyloid fibrils, which have a characteristic beta-pleated sheet structure. Amyloid deposits can be composed of different types of proteins, depending on the specific disease associated with the deposit.
In some cases, amyloid deposits can cause damage to organs and tissues, leading to various clinical symptoms. Some examples of diseases associated with amyloidosis include Alzheimer's disease (where amyloid-beta protein accumulates in the brain), systemic amyloidosis (where amyloid fibrils deposit in various organs such as the heart, kidneys, and liver), and type 2 diabetes (where amyloid deposits form in the pancreas).
It's important to note that not all amyloid deposits are harmful or associated with disease. However, when they do cause problems, treatment typically involves managing the underlying condition that is leading to the abnormal protein accumulation.
Diabetic neuropathies refer to a group of nerve disorders that are caused by diabetes. High blood sugar levels can injure nerves throughout the body, but diabetic neuropathies most commonly affect the nerves in the legs and feet.
There are four main types of diabetic neuropathies:
1. Peripheral neuropathy: This is the most common type of diabetic neuropathy. It affects the nerves in the legs and feet, causing symptoms such as numbness, tingling, burning, or shooting pain.
2. Autonomic neuropathy: This type of neuropathy affects the autonomic nerves, which control involuntary functions such as heart rate, blood pressure, digestion, and bladder function. Symptoms may include dizziness, fainting, digestive problems, sexual dysfunction, and difficulty regulating body temperature.
3. Proximal neuropathy: Also known as diabetic amyotrophy, this type of neuropathy affects the nerves in the hips, thighs, or buttocks, causing weakness, pain, and difficulty walking.
4. Focal neuropathy: This type of neuropathy affects a single nerve or group of nerves, causing symptoms such as weakness, numbness, or pain in the affected area. Focal neuropathies can occur anywhere in the body, but they are most common in the head, torso, and legs.
The risk of developing diabetic neuropathies increases with the duration of diabetes and poor blood sugar control. Other factors that may contribute to the development of diabetic neuropathies include genetics, age, smoking, and alcohol consumption.
Amyloid beta-peptides (Aβ) are small protein fragments that are crucially involved in the pathogenesis of Alzheimer's disease. They are derived from a larger transmembrane protein called the amyloid precursor protein (APP) through a series of proteolytic cleavage events.
The two primary forms of Aβ peptides are Aβ40 and Aβ42, which differ in length by two amino acids. While both forms can be harmful, Aβ42 is more prone to aggregation and is considered to be the more pathogenic form. These peptides have the tendency to misfold and accumulate into oligomers, fibrils, and eventually insoluble plaques that deposit in various areas of the brain, most notably the cerebral cortex and hippocampus.
The accumulation of Aβ peptides is believed to initiate a cascade of events leading to neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal death, which are all hallmarks of Alzheimer's disease. Although the exact role of Aβ in the onset and progression of Alzheimer's is still under investigation, it is widely accepted that they play a central part in the development of this debilitating neurodegenerative disorder.
Serum Amyloid A (SAA) protein is an acute phase protein produced primarily in the liver, although it can also be produced by other cells in response to inflammation. It is a member of the apolipoprotein family and is found in high-density lipoproteins (HDL) in the blood. SAA protein levels increase rapidly during the acute phase response to infection, trauma, or tissue damage, making it a useful biomarker for inflammation.
In addition to its role as an acute phase protein, SAA has been implicated in several disease processes, including atherosclerosis and amyloidosis. In amyloidosis, SAA can form insoluble fibrils that deposit in various tissues, leading to organ dysfunction. There are four subtypes of SAA in humans (SAA1, SAA2, SAA3, and SAA4), with SAA1 and SAA2 being the most responsive to inflammatory stimuli.
Peripheral Nervous System (PNS) diseases, also known as Peripheral Neuropathies, refer to conditions that affect the functioning of the peripheral nervous system, which includes all the nerves outside the brain and spinal cord. These nerves transmit signals between the central nervous system (CNS) and the rest of the body, controlling sensations, movements, and automatic functions such as heart rate and digestion.
PNS diseases can be caused by various factors, including genetics, infections, toxins, metabolic disorders, trauma, or autoimmune conditions. The symptoms of PNS diseases depend on the type and extent of nerve damage but often include:
1. Numbness, tingling, or pain in the hands and feet
2. Muscle weakness or cramps
3. Loss of reflexes
4. Decreased sensation to touch, temperature, or vibration
5. Coordination problems and difficulty with balance
6. Sexual dysfunction
7. Digestive issues, such as constipation or diarrhea
8. Dizziness or fainting due to changes in blood pressure
Examples of PNS diseases include Guillain-Barre syndrome, Charcot-Marie-Tooth disease, diabetic neuropathy, and peripheral nerve injuries. Treatment for these conditions varies depending on the underlying cause but may involve medications, physical therapy, lifestyle changes, or surgery.
The Amyloid Beta-Protein Precursor (AβPP) is a type of transmembrane protein that is widely expressed in various tissues and organs, including the brain. It plays a crucial role in normal physiological processes, such as neuronal development, synaptic plasticity, and repair.
AβPP undergoes proteolytic processing by enzymes called secretases, resulting in the production of several protein fragments, including the amyloid-beta (Aβ) peptide. Aβ is a small peptide that can aggregate and form insoluble fibrils, which are the main component of amyloid plaques found in the brains of patients with Alzheimer's disease (AD).
The accumulation of Aβ plaques is believed to contribute to the neurodegeneration and cognitive decline observed in AD. Therefore, AβPP and its proteolytic processing have been the focus of extensive research aimed at understanding the pathogenesis of AD and developing potential therapies.
Amyloid plaque is a pathological hallmark of several degenerative diseases, including Alzheimer's disease. It refers to extracellular deposits of misfolded proteins that accumulate in various tissues and organs, but are most commonly found in the brain. The main component of these plaques is an abnormally folded form of a protein called amyloid-beta (Aβ). This protein is produced through the normal processing of the amyloid precursor protein (APP), but in amyloid plaques, it aggregates into insoluble fibrils that form the core of the plaque.
The accumulation of amyloid plaques is thought to contribute to neurodegeneration and cognitive decline in Alzheimer's disease and other related disorders. The exact mechanisms by which this occurs are not fully understood, but it is believed that the aggregation of Aβ into plaques leads to the disruption of neuronal function and viability, as well as the activation of inflammatory responses that can further damage brain tissue.
It's important to note that while amyloid plaques are a key feature of Alzheimer's disease, they are not exclusive to this condition. Amyloid plaques have also been found in other neurodegenerative disorders, as well as in some normal aging brains, although their significance in these contexts is less clear.
Hereditary Sensory and Motor Neuropathy (HSMN) is a group of inherited disorders that affect the peripheral nerves, which are the nerves outside the brain and spinal cord. These nerves transmit information between the brain and muscles, as well as sensations such as touch, pain, heat, and cold.
HSMN is characterized by progressive degeneration of these peripheral nerves, leading to muscle weakness, numbness, and tingling sensations, particularly in the hands and feet. The condition can also affect the autonomic nervous system, which controls involuntary functions such as heart rate, blood pressure, and digestion.
HSMN is caused by genetic mutations that are inherited from one or both parents. There are several types of HSMN, each with its own specific symptoms, severity, and pattern of inheritance. The most common form is Charcot-Marie-Tooth disease (CMT), which affects both motor and sensory nerves.
Treatment for HSMN typically focuses on managing the symptoms and preventing complications. This may include physical therapy, bracing or orthopedic surgery to support weakened muscles, pain management, and lifestyle modifications such as avoiding activities that aggravate symptoms. There is currently no cure for HSMN, but ongoing research is aimed at developing new treatments and therapies to slow or halt the progression of the disease.
Islet Amyloid Polypeptide (IAPP), also known as amylin, is a 37-amino acid peptide co-secreted with insulin from pancreatic beta-cells in response to meals. It plays crucial roles in regulating glucose homeostasis by suppressing glucagon secretion, slowing gastric emptying, and promoting satiety. In type 2 diabetes, IAPP can form amyloid fibrils, which deposit in pancreatic islets, contributing to beta-cell dysfunction and death. This contributes to the progressive nature of type 2 diabetes.
Cerebral amyloid angiopathy (CAA) is a medical condition characterized by the accumulation of beta-amyloid protein in the walls of small to medium-sized blood vessels in the brain. This protein buildup can cause damage to the vessel walls, leading to bleeding (cerebral hemorrhage), cognitive decline, and other neurological symptoms.
CAA is often associated with aging and is a common finding in older adults. It can also be seen in people with Alzheimer's disease and other forms of dementia. The exact cause of CAA is not fully understood, but it is believed to result from the abnormal processing and clearance of beta-amyloid protein in the brain.
The diagnosis of CAA typically involves a combination of clinical evaluation, imaging studies such as MRI or CT scans, and sometimes cerebrospinal fluid analysis. Treatment for CAA is generally supportive and focused on managing symptoms and preventing complications. There are currently no approved disease-modifying treatments for CAA.
Hereditary Sensory and Autonomic Neuropathies (HSANs) are a group of inherited disorders that affect the sensory and autonomic nerves. These nerves are responsible for transmitting information about senses such as touch, pain, temperature, and vibration to the brain, as well as controlling automatic functions like blood pressure, heart rate, and digestion.
HSANs are caused by genetic mutations that result in damage to the peripheral nerves. There are several types of HSANs, each with its own specific symptoms and patterns of inheritance. Some common features include:
* Loss of sensation in the hands and feet
* Pain insensitivity
* Absent or reduced reflexes
* Autonomic dysfunction, such as abnormal sweating, blood pressure regulation, and digestive problems
The severity and progression of HSANs can vary widely depending on the specific type and individual factors. Treatment is generally focused on managing symptoms and preventing complications, such as injuries from lack of pain sensation or falls due to balance problems. Early diagnosis and intervention are important for optimizing outcomes.
Ischemic optic neuropathy (ION) is a medical condition that refers to the damage or death of the optic nerve due to insufficient blood supply. The optic nerve is responsible for transmitting visual information from the eye to the brain.
In ION, the blood vessels that supply the optic nerve become blocked or narrowed, leading to decreased blood flow and oxygen delivery to the nerve fibers. This results in inflammation, swelling, and ultimately, damage to the optic nerve. The damage can cause sudden, painless vision loss, often noticed upon waking up in the morning.
There are two types of ION: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION affects the front part of the optic nerve, while PION affects the back part of the nerve. AION is further classified into arteritic and non-arteritic types, depending on whether it is caused by giant cell arteritis or not.
Risk factors for ION include age (most commonly occurring in people over 50), hypertension, diabetes, smoking, sleep apnea, and other cardiovascular diseases. Treatment options depend on the type and cause of ION and may include controlling underlying medical conditions, administering corticosteroids, or undergoing surgical procedures to improve blood flow.
Serum Amyloid P-component (SAP) is a protein that is normally present in the blood and other bodily fluids. It is a part of the larger family of pentraxin proteins, which are involved in the innate immune response, meaning they provide immediate defense against foreign invaders without needing to adapt over time. SAP plays a role in inflammation, immune complex clearance, and complement activation.
In the context of amyloidosis, SAP binds to misfolded proteins called amyloid fibrils, which can deposit in various tissues and organs, leading to their dysfunction and failure. The accumulation of these amyloid fibrils with SAP is a hallmark of systemic amyloidosis.
It's important to note that while SAP plays a role in the pathogenesis of amyloidosis, it is not directly responsible for causing the disease. Instead, its presence can serve as a useful marker for diagnosing and monitoring the progression of amyloidosis.
Polyneuropathy is a medical condition that refers to the damage or dysfunction of peripheral nerves (nerves outside the brain and spinal cord) in multiple areas of the body. These nerves are responsible for transmitting sensory, motor, and autonomic signals between the central nervous system and the rest of the body.
In polyneuropathies, this communication is disrupted, leading to various symptoms depending on the type and extent of nerve damage. Commonly reported symptoms include:
1. Numbness or tingling in the hands and feet
2. Muscle weakness and cramps
3. Loss of reflexes
4. Burning or stabbing pain
5. Balance and coordination issues
6. Increased sensitivity to touch
7. Autonomic dysfunction, such as bowel, bladder, or digestive problems, and changes in blood pressure
Polyneuropathies can be caused by various factors, including diabetes, alcohol abuse, nutritional deficiencies, autoimmune disorders, infections, toxins, inherited genetic conditions, or idiopathic (unknown) causes. The treatment for polyneuropathy depends on the underlying cause and may involve managing underlying medical conditions, physical therapy, pain management, and lifestyle modifications.
The sural nerve is a purely sensory peripheral nerve in the lower leg and foot. It provides sensation to the outer ( lateral) aspect of the little toe and the adjacent side of the fourth toe, as well as a small portion of the skin on the back of the leg between the ankle and knee joints.
The sural nerve is formed by the union of branches from the tibial and common fibular nerves (branches of the sciatic nerve) in the lower leg. It runs down the calf, behind the lateral malleolus (the bony prominence on the outside of the ankle), and into the foot.
The sural nerve is often used as a donor nerve during nerve grafting procedures due to its consistent anatomy and relatively low risk for morbidity at the donor site.
Amyloid precursor protein (APP) secretases are enzymes that are responsible for cleaving the amyloid precursor protein into various smaller proteins. There are two types of APP secretases: α-secretase and β-secretase.
α-Secretase is a member of the ADAM (a disintegrin and metalloproteinase) family, specifically ADAM10 and ADAM17. When APP is cleaved by α-secretase, it produces a large ectodomain called sAPPα and a membrane-bound C-terminal fragment called C83. This pathway is known as the non-amyloidogenic pathway because it prevents the formation of amyloid-β (Aβ) peptides, which are associated with Alzheimer's disease.
β-Secretase, also known as β-site APP cleaving enzyme 1 (BACE1), is a type II transmembrane aspartic protease. When APP is cleaved by β-secretase, it produces a large ectodomain called sAPPβ and a membrane-bound C-terminal fragment called C99. Subsequently, C99 is further cleaved by γ-secretase to generate Aβ peptides, including the highly neurotoxic Aβ42. This pathway is known as the amyloidogenic pathway because it leads to the formation of Aβ peptides and the development of Alzheimer's disease.
Therefore, APP secretases play a crucial role in the regulation of APP processing and have been the focus of extensive research in the context of Alzheimer's disease and other neurodegenerative disorders.
Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. It's the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.
The early signs of the disease include forgetting recent events or conversations. As the disease progresses, a person with Alzheimer's disease will develop severe memory impairment and lose the ability to carry out everyday tasks.
Currently, there's no cure for Alzheimer's disease. However, treatments can temporarily slow the worsening of dementia symptoms and improve quality of life.