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Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease
Author(s) -
GomezIsla Teresa,
West Howard L.,
Rebeck G. William,
Harr Steven D.,
Growdon John H.,
Locascio Joseph J.,
Perls Thomas T.,
Lipsitz Lewis A.,
Hyman Bradley T.
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410390110
Subject(s) - apolipoprotein e , pathological , dementia , neuropathology , alzheimer's disease , age of onset , genotype , allele , degenerative disease , pathology , psychology , disease , medicine , oncology , biology , genetics , gene
Inheritance of the apolipoprotein E (apoE) ε4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE ε4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty‐one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and Aβ deposits were assessed in a high‐order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the ε4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. Aβ deposition, by contrast, was not related to clinical features but was elevated in association with apoE ε4. These results indicate that apoE ε4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE ε4 on amyloid deposition.