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P2‐132: Drastic impact on Abeta accumulation in APP Tg mice by genetic background
Author(s) -
Yokokoji Mikiko,
Morihara Takashi,
Hayashi Noriyuki,
Tagami Shinji,
Takeda Masatoshi
Publication year - 2009
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.2009.04.443
Subject(s) - ratón , microbiology and biotechnology , medicine , endocrinology , biology
Background: The frequent co-occurrence of Alzheimer’s disease (AD) pathology in patients with clinically diagnosed normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of potentially faulty cerebrospinal fluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of A-beta in CSF in preclinical and early AD. Methods: CSF biomarker data (A-beta, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volume data were obtained from the Alzheimer’s Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 819 subjects classified as being either normal (n1⁄4229), having the syndrome of mild cognitive impairment (n1⁄4397), or mild AD (n1⁄4193). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. Subjects in each diagnostic group were further stratified by ApoE genotype. Results: For controls, ventricular volume was negatively associated with A-beta in E4 positive subjects, independent of age. Ventricular volume as well as age was negatively associated with tau in E4 negative control subjects. A significant reversed pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not A-beta, in E4 positive subjects, independent of age. Abeta and tau were not significantly related to whole brain volume in either controls or AD; however, tau was negatively related to whole brain volume in MCI subjects. Conclusions: Increased ventricular volume may be associated with decreased levels of CSF A-beta in preclinical AD. The basis for the apparent effect of ApoE4 genotype on the relationship of ventricular volume to A-beta and tau levels is unknown, but could involve altered CSF-bloodbrain barrier function early in the course of the disease. Further experimental evidence with animal models of hydrocephalus and ApoE may shed light on the exact nature of these relationships.