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

AimsDeposition of amyloid beta (A) in the brain is one of the defining abnormalities of Alzheimer's disease (AD). Phosphorylation of A at serine 8 (pA) has been implicated in its aggregation in vitro and pA level has been shown to be significantly elevated in AD. We aimed to assess the specificity of pA for AD and have investigated associations of pA with parenchymal and cerebrovascular accumulation of A, disease progression, angiotensin-converting enzyme activity and APOE genotype. MethodsThe distribution of pA 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) pA 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). ResultsWe found pA to be associated with only a subset of A plaques and vascular deposits in sporadic and familial AD, with absent or minimal immunohistochemically detectable pA in control, DLB and VaD brains. In both brain regions, insoluble pA level was significantly elevated only in advanced AD (Braak tangle stage of V or VI) and in the parahippocampus soluble and insoluble pA level increased with the number of APOE epsilon 4 alleles. ConclusionsThese results indicate that pA accumulation in the parenchyma and vasculature is largely restricted to late-stage AD (Braak tangle stage V-VI).