N112a-AlzheimerDisease-2011

N112a-AlzheimerDisea - Alzheimer’s disease I Molecular and cellular approaches N112a Mathew Blurton-Jones [email protected] Memory impairments can

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Unformatted text preview: Alzheimer’s disease I: Molecular and cellular approaches N112a 11/16/11 Mathew Blurton-Jones [email protected] Memory impairments can occur as a part of many disorders • Parkinson Disease • Dementia with Lewy Bodies • Huntington Disease • Traumatic Brian Injury • Stroke • Alzheimer Disease Outline • What is Alzheimer Disease (AD) • AD prevalence, neuropathology • Mouse models of AD • What have AD mouse models taught us? • Alternative approaches to study AD Alois Alzheimer 1864-1915 November 6, 1906 “ A Peculiar Disease of the Cerebral Cortex ” Auguste D Photo dated November, 1902 “I have lost myself.” Alzheimer Disease (AD) • Alzheimer disease is an age-related progressive brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry out daily activities. AD Risk Factors • Advancing age • Susceptibility/risk genes • Family history of dementia • Previous head trauma • Low education level • Down syndrome • Diet and other environmental factors Why is the incidence of Alzheimer’s disease increasing so much? Year 5 10 15 20 25 2050 2020 1990 1960 1930 1900 4.1% 5.4% 9.2% 12.6% 17.7% 22.9% Percent of Population 5 10 15 20 25 Growth of Population Sixty-five Years Old and Over AD Neuropathology • Amyloid Plaques: 40-42 amino acid -amyloid peptide (A ) • Neurofibrillary Tangles: hyperphosphorylated tau Plaques and tangles (shown in the blue-shaded areas) tend to spread through the cortex in a predictable pattern as Alzheimer’s disease progresses. Earliest Alzheimer's – changes may begin 20 years or more before diagnosis. Mild to moderate Alzheimer stages – generally last from 2 - 10 years. Severe Alzheimer’s – may last from 1 - 5 years Slide from The Alzheimer’s Association A is produced via the Sequential Proteolysis of the Amyloid Precursor Protein (APP) Rare mutations in APP or Presenilin cause early-onset familial AD Genetics of Alzheimer Disease risk factor Aß deposits 60+ ~40% 3 alleles: 2, 3, 4 19 ApoE autosomal dominant Aß 42 60+ < 0.1 8 1 PS2 autosomal...
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This note was uploaded on 12/13/2011 for the course BIOSCI 93 taught by Professor Staff during the Fall '11 term at UC Irvine.

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N112a-AlzheimerDisea - Alzheimer’s disease I Molecular and cellular approaches N112a Mathew Blurton-Jones [email protected] Memory impairments can

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