Mann D M, Iwatsubo T, Nochlin D, Sumi S M, Levy-Lahad E, Bird T D
Department of Pathological Sciences, University of Manchester, UK.
Ann Neurol. 1997 Jan;41(1):52-7. doi: 10.1002/ana.410410110.
Amyloid beta protein (Abeta) 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 Abeta40 and Abeta42(43), respectively. In all patients, Abeta42(43) was the predominant peptide species present, although the total amount of Abeta40 and Abeta42(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 Abeta42(43) within the brain. Although the mechanism(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 Abeta 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.
