ABSTRACT


Objective: Plasma Aβ levels are elevated in early onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late onset AD (LOAD).


Methods: We measured plasma Aβ in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early onset AD genes and determined their ApoE genotypes.


Results: Plasma Aβ is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE 4 or pathogenic coding mutations in the known early onset AD genes.


Conclusions: The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late onset Alzheimer disease by increasing Aβ.

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