Journal ArticleDOI
Synaptic pathology in Alzheimer's disease: relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele.
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TLDR
No significant differences in rab3a levels were found in any brain region between AD patients possessing different numbers of the apolipoprotein E4 allele, suggesting that, although ApoE4 is a risk factor for earlier development of AD, the degree of synaptic pathology does not differ between patients with or without the ApOE4 allele.Abstract:
Alzheimer's disease (AD) is characterised by an increased number of senile plaques (SP) and neuroflbrillary tangles (NFT) as compared with that found in non-demented individuals of the same age, and a marked degeneration and loss of synapses. One of the main risk-factors for the disorder is inheritance of the apolipoprotein E4 (ApoE4) allele. To further study the relation between these pathogenetic substrates for AD, we quantified the synaptic vesicle membrane protein rab3a in brain tissue from 19 patients with AD and 9 age-matched control subjects. Rab3a levels were reduced in AD, both in the hippocampus (60% of control level, p < 0.0001), and in the frontal cortex (68% of control level, p < 0.01), but not in the cerebellum (92% of control level). Within the AD group, lower rab3a levels were found both with increasing duration and severity of dementia. These findings further support that synaptic pathology is closely correlated to the clinical dementia in AD. In contrast, no significant correlations were found between SP counts and duration or severity of dementia, while higher NFT counts in the frontal cortex were found with increasing severity of dementia (r=0.54, p < 0.05). There were no significant correlations between the rab3a level and SP or NFT counts, and by immunohistochemistry, reduced rab3a immunostaining was found throughout the neuropil in AD brain, without relation to SP or NFT. These findings suggest that the synaptic pathology in AD is not closely related to the presence of SP and NFT. No significant differences in rab3a levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele, suggesting that, although ApoE4 is a risk factor for earlier development of AD, the degree of synaptic pathology does not differ between patients with or without the ApoE4 allele.read more
Citations
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Journal ArticleDOI
Clearance systems in the brain—implications for Alzheimer disease
Jenna M. Tarasoff-Conway,Roxana O. Carare,Ricardo S. Osorio,Lidia Glodzik,Tracy Butler,Els Fieremans,Leon Axel,Henry Rusinek,Charles Nicholson,Berislav V. Zlokovic,Blas Frangione,Kaj Blennow,Joël Ménard,Henrik Zetterberg,Thomas Wisniewski,Mony J. de Leon +15 more
TL;DR: The clearance systems of the brain as they relate to proteins implicated in AD pathology are described, with the main focus on Aβ.
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Biomarkers for Alzheimer's disease: current status and prospects for the future.
Kaj Blennow,Henrik Zetterberg +1 more
TL;DR: Technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis and neurodegeneration in plasma samples and one promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration.
Journal ArticleDOI
Synaptic degeneration in Alzheimer’s disease
TL;DR: The hypothesis that differentiated neurons after having withdrawn from the cell cycle are able to use molecular mechanisms primarily developed to control proliferation alternatively to control synaptic plasticity is formulated and a role for diffusible oligomers of amyloid β in synaptic dysfunction is suggested.
Journal ArticleDOI
Alzheimer's disease: connecting findings from graph theoretical studies of brain networks
Betty M. Tijms,Alle Meije Wink,Willem de Haan,Wiesje M. van der Flier,Cornelis J. Stam,Philip Scheltens,Frederik Barkhof +6 more
TL;DR: This work examined which graph properties have been consistently reported to be disturbed in AD studies, using a heuristically defined "graph space" to investigate which theoretical models can best explain graph alterations in AD.
Journal ArticleDOI
Differential loss of synaptic proteins in Alzheimer's disease: implications for synaptic dysfunction.
P. Hemachandra Reddy,Geethalakshmi Mani,Byung Park,Joline Jacques,Geoffrey Murdoch,William O. Whetsell,Jeffrey Kaye,Maria Manczak +7 more
TL;DR: It is suggested that postsynaptic proteins and presynaptic proteins are important for synaptic function and may be related to cognitive impairments in AD.
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