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P1‐197: Decreased brain supply of blood in non‐demented elderly with APOE4 alleles
Author(s) -
Sorensen Katrine N.,
Jorgensen Ole S.
Publication year - 2010
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.2010.05.747
Subject(s) - apolipoprotein e , albumin , medicine , neuropathology , hippocampus , allele , temporal cortex , alzheimer's disease , endocrinology , chemistry , biology , biochemistry , disease , neuroscience , gene
Background: The role of APOE4 alleles as a major risk factor for Alzheimer disease is poorly understood. Methods: The studied subjects were brain donors to the Netherlands Brain Bank(mean post mortal delay 5.4 6 0.8 hours). Both normal controls without neuropathology (CON; N1⁄4 167, mean age 74.8 6 1.0 years) and Alzheimer disease patients (AD; N1⁄4 259, 80.0 6 0.6 years) were investigated. From each subject, only a single area of the brain was used. One gram, mainly grey matter, was pulverized below liquid nitrogen. APOE genotypes were determined by restriction enzyme analysis of PCR enhanced DNA, and grouped as APOE4and APOE4+. Albumin concentrations were determined by routine clinical analysis and expressed as mg albumin/g brain tissue. Results: The brain areas studied were cerebellum (CBL), frontal cortex (FC), temporal cortex (TC), and hippocampus (HIP). In CON the concentration of albumin was higher in CBL (mean 6 SEM: 0.59 6 0.01mg/g) compared to the other brain areas (0.33-0.37mg/g). In all areas the concentration of albumin was higher in AD compared to CON (12-19 %), possibly indicating a break down of the BBB in AD.In AD no difference was found between albumin concentrations in APOE4and APOE4+. However, in CON, the albumin concentration was decreased in APOE4+ compared to APOE4in all brain areas. In CBL it was from 0.60 6 0.06 to 0.58 6 0.10 mg/g, in FC it was from 0.35 6 0.02 to 0.30 6 0.02 mg/g, in TC it was from 0.38 6 0.03 to 0.27 6 0.04 mg/g, and in HIP it was from 0.35.0 6 0.02 to 0.26 6 0.03 mg/g. The averaged decrease was 18 %. Conclusions: The concentration of albumin in the brain samples probably reflects the amount of blood trapped in the rapidly frozen brain tissue. It can be calculated that the amount of blood trapped in the CON brain with APOE4was close to 1% but significantly less in CON brain with APOE4+ alleles. Our finding suggest a lack of blood supply in elderly with APOE4+ genotypes. The finding may have implications for understanding why APOE4+ is a risk factor for developing AD, and it may also contribute to understanding the general pathogenesis of late onset AD.