title: Investigation of Aβ phosphorylated at serine 8 (pAβ) in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results indicate that pAβ accumulation in the parenchyma and vasculature is largely restricted to late-stage AD (Braak tangle stage V-VI).
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Ashby
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: James S
authors.initials: JS
authors.lastname: Miners
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Sathish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Walter
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Level 1 Learning and Research, Southmead Hospital, Bristol, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D015140:Dementia, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016631:Lewy Bodies; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D012694:Serine
keywords: Alzheimer's disease; amyloid β protein; dementia with Lewy bodies; phosphorylation; vascular dementia