Investigation of Aβ phosphorylated at serine 8 (pAβ) in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.

Emma L Ashby, James S Miners, Sathish Kumar, Jochen Walter, Seth Love, Patrick G Kehoe

Index: Neuropathol. Appl. Neurobiol. 41 , 428-44, (2015)

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Abstract

Deposition of amyloid beta (Aβ) in the brain is one of the defining abnormalities of Alzheimer's disease (AD). Phosphorylation of Aβ at serine 8 (pAβ) has been implicated in its aggregation in vitro and pAβ level has been shown to be significantly elevated in AD. We aimed to assess the specificity of pAβ for AD and have investigated associations of pAβ with parenchymal and cerebrovascular accumulation of Aβ, disease progression, angiotensin-converting enzyme activity and APOE genotype.The distribution of pAβ was studied by immunohistochemistry in sporadic and familial AD, pure dementia with Lewy bodies (DLB), pure vascular dementia (VaD) and age-matched controls. Soluble and insoluble (guanidine-extractable) pAβ level was measured by enzyme-linked immunosorbent assay (ELISA) in the midfrontal and parahippocampal cortex in sporadic AD (n = 20, 10 with Braak tangle stages of III-IV and 10 of stages V-VI), DLB (n = 10), VaD (n = 10) and age-matched controls (n = 20).We found pAβ to be associated with only a subset of Aβ plaques and vascular deposits in sporadic and familial AD, with absent or minimal immunohistochemically detectable pAβ in control, DLB and VaD brains. In both brain regions, insoluble pAβ level was significantly elevated only in advanced AD (Braak tangle stage of V or VI) and in the parahippocampus soluble and insoluble pAβ level increased with the number of APOE ε4 alleles.These results indicate that pAβ accumulation in the parenchyma and vasculature is largely restricted to late-stage AD (Braak tangle stage V-VI).© 2014 British Neuropathological Society.