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PL‐04‐03: Function and dysfunction of presenilins
Author(s) -
Thinakaran Gopal
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.470
Subject(s) - presenilin , amyloid precursor protein , psen1 , amyloid precursor protein secretase , nicastrin , endoplasmic reticulum , biology , transmembrane protein , notch signaling pathway , gene , transmembrane domain , microbiology and biotechnology , genetics , alzheimer's disease , disease , medicine , receptor , pathology
Background: (1) Population-based studies show that late onset Alzheimer’s Disease (AD) has a large heritable component (about 60%) with environmental factors accounting for the remaining 40% of the variance. (2) The location and extent of Alzheimer-type pathology varies substantially among individuals with similar degrees of mental impairment. Genetic factors do not account for these discrepancies. (3) Environmental risk factors are not well-characterized; for AD these include low education and childhood mental ability. (4) These two risk factors are also associated with greater mortality and raised incidences of many age-related diseases including dementia. The studies summarized here examine possible mechanisms linking childhood mental ability to increased dementia risk and ask how specific this link is to dementia compared to other age-related disorders. Methods: The Scottish Mental Surveys (SMS) of 1932 and 1947 systematically surveyed all children at school in Scotland born in 1921 or 1936 and at school on 1 June 1932 or 4 June 1947. From 1998, these children were followed up in Aberdeen, Scotland. Mortality, dementia incidence and age-related cognitive decline were measured using standardized methods in SMS 1921 annually from 1998-2004. From 2000, these were measured biennially in SMS47 . Neuroimaging was repeated in selected sub-samples. Nutritional and genetic studies were completed on recruitment. Results: Childhood intelligence (IQ) and low educational attainments are linked to adult health by several pathways. Childhood IQ is associated, for example, with certain health behaviors: smoking cessation but not initiation and poor dietary habits but not obesity. Greater than expected rates of cognitive decline; sub-optimal social support ; greater mortality and more dementia are also associated with childhood IQ. Indices of poor cardiovascular and respiratory health (including B12/folate metabolism) were also linked to childhood IQ. Statistical modeling of these associations suggest that IQ and education make shared and non-shared contributions to disease risk some of which may be mediated through sex and nutritional differences. Conclusions: Associations between childhood IQ and dementia are non-specific and, like associations between education and greater adult disease morbidity, may share common ground with socio-economic status, some health behaviors and, potentially, life-long use of health services.