Amyloid (Aβ) deposition in chromosome 1–linked Alzheimer's disease: The volga german families

Amyloid β protein (Aβ) deposition was investigated in the frontal cortex of 6 cases of (genetically confirmed) chromosome 1–linked Alzheimer's disease (AD) (PS‐2 gene mutation) among the Volga German families using the end‐specific monoclonal antibodies BA27 and BC05 to detect the presence of Aβ40 and Aβ42(43), respectively. In all patients, Aβ42(43) was the predominant peptide species present, although the total amount of Aβ40 and Aβ42(43) deposited in plaques did not differ from that seen in sporadic AD and was significantly lower than that occurring in AD due to PS‐1 gene mutations. Therefore, mutations in the PS‐2 gene, like those in the presenilin‐1 (PS‐1) and amyloid precursor protein (APP) genes, are associated with an initial and preferential deposition of Aβ42(43) within the brain. Although the mechanisms(s) whereby the PS‐1 and PS‐2 gene mutations operate remains unclear, it seems from the present study that the effect of the PS‐2 gene mutation on the brain is muuch less severe, at least as far as Aβ deposition is concerned, than that of the PS‐1 mutation, which seems to confer a much earlier and a much more aggressive development of AD.

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