disease (AD) is a progressive neurodegenerative disorder of the central nervous system leading to the most common form of age-associated dementia. the biological factors involved in AD started in the early 1980s with Bexarotene the first efforts to elucidate the molecular nature of the neuropathological markers found in the brains of affected individuals. These markers include neuritic amyloid plaques neurofibrillary tangles and cerebrovascular amyloidosis. Interestingly a volume on a symposium on amyloid and amyloidosis held in 1979 makes no reference to the amyloidosis of AD 1 and this indicates that even at this late date there was little effort directed Rabbit Polyclonal to MYLIP. at the neuropathology of AD. Neuritic amyloid plaques are complex extracellular structures made up of at their core amyloid deposits of fibrillar amyloid beta (Apeptides in brain blood vessels; this condition is usually termed because they lack a clear genetic etiology but about 5% of all cases display clear genetic linkages and are classified as familial Alzheimer’s disease (FAD). These usually occur at younger ages and follow a more aggressive clinical course than the sporadic forms of AD. Bexarotene The brain neuropathology however is similar in sporadic AD and FAD and this suggests the involvement of common cellular mechanisms in all AD cases. Despite intense efforts there is still no chemical test to assay for AD and because clinical symptoms similar to those of AD may be caused by a number of conditions or diseases including Bexarotene vascular dementia a definite diagnosis of AD is possible only after clinical symptoms are combined with a postmortem examination of brain tissue for the detection of plaques and tangles. In this volume Daniel Perl gives a comprehensive review of the neuropathological and clinical findings that characterize AD. Although in the last quarter of a century we have learned a great deal about this disease including the chemical composition of the neuropathological markers of AD and information about the genetics of this disorder the main mechanisms responsible for the accelerated neuronal cell loss that results in dementia are still poorly Bexarotene understood. It is generally accepted however that like the pathogenesis of many other disorders the pathogenesis of AD is usually complex driven by both environmental and genetic factors. Presently aging and the gene encoding apolipoprotein allele E42 are the two largest known risk factors for sporadic AD. In contrast to sporadic AD FAD is mostly driven by specific genetic mutations localized in at least 3 distinct genes including those encoding the amyloid precursor protein (APP) Presenilin 1 and Presenilin 2. APP is usually important to all forms of AD because in addition to its specific involvement in the development of FAD APP is the precursor of the Apeptides that aggregate to form the deposits of amyloid fibrils used to define this disorder. APP is also important to the neuropathology of Down syndrome because patients over the age of 40 years develop amyloid deposits identical to those found in patients with AD. Localization of the APP gene on chromosome 21 revealed a direct genetic linkage between these two disorders.3 A common theory posits that amyloid deposits of Afibrils or soluble Bexarotene oligomeric forms of Apeptides are the main causes of the neurodegeneration of AD.4 There are several weaknesses to this theory however including studies that show no significant correlation between brain amyloid loads and degree of dementia and data indicating that soluble Aspecies become toxic only at concentrations ten of thousand times higher than their concentrations (for recent review of involvement of Aand derivatives in AD see ref. 5). There are several weaknesses to this theory however including studies that show no significant correlation between the brain amyloid loads and the degree of dementia. Furthermore soluble Apeptides are normal components of human serum and cerebrospinal fluid and presently there is usually little evidence of disease-associated changes in soluble Aor its oligomeric forms. In this volume Gandy and Lublin give a critical review of the involvement of soluble Oligomers in the development of AD. Recent findings indicate that dysfunctions of the cerebrovascular system caused by cerebrovascular amyloidosis oxidative stress and genetics may play important roles in the pathogenesis of AD. Dickstein and colleagues offer an extensive analysis of factors that may promote cerebrovascular abnormalities and their potential involvement in.