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 Aβ(42(43)), respectively. In all patients, Aβ(42(43)) was the predominant peptide species present, although the total amount of Aβ₄₀ and Aβ(42(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 Aβ(42(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 much 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.