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Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease
Author(s) -
Mizukami Katsuyoshi,
Akatsu Hiroyasu,
Abrahamson Eric E.,
Mi Zhiping,
Ikonomovic Milos D.
Publication year - 2016
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12241
Subject(s) - butyrylcholinesterase , senile plaques , acetylcholinesterase , hippocampal formation , dentate gyrus , alzheimer's disease , pathology , hippocampus , locus coeruleus , amyloid (mycology) , medicine , neuroscience , biology , endocrinology , chemistry , aché , biochemistry , central nervous system , disease , enzyme
Studies of acetylcholine degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in Alzheimer's disease (AD) have suggested their potential role in the development of fibrillar amyloid‐β (Aβ) plaques (amyloid plaques). A recent genome‐wide association study analysis identified a novel association between genetic variations in the BCHE locus and amyloid burden. We studied BChE immunoreactivity in hippocampal tissue sections from AD and control cases, and examined its relationship with amyloid plaques, neurofibrillary tangles (NFT), dystrophic neurites (DN) and neuropil threads (NT). Compared to controls, AD cases had greater BChE immunoreactivity in hippocampal neurons and neuropils in CA2/3, but not in the CA1, CA4 and dentate gyrus. The majority of amyloid plaques (> 80%, using a pan‐amyloid marker X‐34) contained discrete neuritic clusters which were dual‐labeled with antibodies against BChE and phosphorylated tau (clone AT8). There was no association between overall regional BChE immunoreaction intensity and amyloid plaque burden. In contrast to previous reports, BChE was localized in only a fraction (~10%) of classic NFT (positive for X‐34). A similar proportion of BChE‐immunoreactive pyramidal cells were AT8 immunoreactive. Greater NFT and DN loads were associated with greater BChE immunoreaction intensity in CA2/3, but not in CA1, CA4 and dentate gyrus. Our results demonstrate that in AD hippocampus, BChE accumulates in neurons and plaque‐associated neuritic clusters, but only in a small proportion of NFT. The association between greater neurofibrillary pathology burden and markedly increased BChE immunoreactivity, observed selectively in CA2/3 region, could reflect a novel compensatory mechanism. Since CA2/3 is generally considered more resistant to AD pathology, BChE upregulation could impact the cholinergic modulation of glutamate neurotransmission to prevent/reduce neuronal excitotoxicity in AD hippocampus.