Espectros generales de alzhai

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Genet Med. Author manuscript; available in PMC 2009 June 3.
Published in final edited form as: Genet Med. 2008 April ; 10(4): 231–239. doi:10.1097/GIM.0b013e31816b64dc.

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Genetic Aspects of Alzheimer Disease
Thomas D Bird, MD University of Washington, Geriatric Research Educationand Clinical Center, VA Puget Sound Health Care System, Seattle, Washington

Alzheimer’s disease (AD) is the most common cause of dementia and represents a major public health problem. The neuropathological findings of Aβ amyloid plaques and tau containing neurofibrillary tangles represent important molecular clues to the underlying pathogenesis. Genetic factors are well recognized,but complicated. Three rare forms of autosomal dominant early onset familial AD have been identified and are associated with mutations in APP (amyloid precursor protein), PS1 (presenilin 1) and PS2 (presenilin 2) genes. The more common late onset form of AD is assumed to be polygenic/multifactorial. However, thus far the only clearly identified genetic risk factor for AD is Apo lipoprotein E. Theε4 allele of ApoE influences age at onset of AD, but is neither necessary nor sufficient for the disease. The search continues for the discovery of additional genetic influences.

Keywords Alzheimer; Dementia; Amyloid; Neurogenetics

Clinical Manifestations of Alzheimer Disease The clinical manifestation of Alzheimer disease (AD) is dementia that typically begins with subtle andpoorly recognized failure of memory and slowly becomes more severe and, eventually, incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations. Occasionally, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism occur1. Death usually results from general inanition, malnutrition, andpneumonia. The typical clinical duration of the disease is eight to ten years, with a range of from one to 25 years. Establishing the Diagnosis of Alzheimer Disease Establishing the diagnosis of Alzheimer disease relies upon clinical-neuropathologic assessment1. Neuropathologic findings on autopsy examination remain the gold standard for

e-mail: E-mail: Resources,Alzheimer’s Association National Headquarters, 225 North Michigan Avenue Fl 17, Chicago IL 60601-7633, Phone: 800-272-3900; 312-335-8700, Fax: 312-335-1110, Email:, Alzheimer’s Disease Education and Referral Center, PO Box 8250, Silver Spring MD 20907-8250, Phone: 800-438-4380; 301-495-3334, Fax: 301-495-3334, Email:, National Library ofMedicine Genetics Home Reference, Alzheimer Disease NCBI Genes and Disease, Alzheimer Disease National Institute on Aging, Building 31 Room 5C27, 31 Center Drive MSC 2292, Bethesda MD 20892, Phone: 301-496-1752, Email:,


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diagnosis of AD. The clinical diagnosis of AD (prior to autopsy confirmation) is correct about 80%-90% of the time2. • Clinicalsigns: slowly progressive dementia • • Neuroimaging: gross cerebral cortical atrophy3 Neuropathologic findings: microscopic extracellular Aβ-amyloid neuritic plaques, intraneuronal neurofibrillary tangles, and amyloid angiopathy at postmortem examination. The plaques should stain positively with Aβ-amyloid antibodies and negative for prion antibodies, which are diagnostic of prion diseases. Thenumbers of plaques and tangles must exceed those found in age-matched controls without dementia. Guidelines for the quantitative assessment of these changes exist4, 5. Aggregation of alpha-synuclein in the form of Lewy bodies may also be found in neurons in the amygdala6.

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Differential Diagnosis of Alzheimer...
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