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Lewy body variant of Alzheimer's disease: selective neocortical loss of t-SNARE proteins and loss of MAP2 and alpha-synuclein in medial temporal lobe
- Source :
- The Scientific World Journal, The Scientific World Journal, Vol 9, Pp 1463-1475 (2009)
- Publication Year :
- 2009
-
Abstract
- Lewy bodies (LBs) appear in the brains of nondemented individuals and also occur in a range of neurodegenerative disorders, such as dementia with Lewy bodies (DLB) and Parkinson's disease. A number of people with a definite diagnosis of Alzheimer's disease (AD) also exhibit these intraneuronal inclusions in allo- and/or neocortical areas. The latter, referred to as Lewy body variant of AD (LBV), bears a clinical resemblance to AD in terms of age at onset, duration of illness, cognitive impairment, and illness severity. Since the presence of LBs is accompanied by neuronal cytoskeleton changes, it is possible that the latter may influence neuronal connectivity via alterations to the synaptic network. To address this, we examined the expression of synaptic proteins (synaptophysin, syntaxin, SNAP-25, and α-synuclein) and two cytoskeletal proteins (tau and MAP2) in the brain tissue of subjects enrolled in a population-based autopsy study (n = 47). They were divided into groups with no memory problems (control group, n = 15), LBV (n = 5), AD devoid of LBs (n = 17), cerebrovascular dementia (n = 3), and mixed dementia (n = 7). The LBV and AD groups had a similar degree of cognitive impairment and neuropathological staging in terms of Braak staging and CERAD score. In comparison with the control group and the dementia groups without LBs, the LBV group had significantly lower levels of syntaxin and SNAP-25 (23%) in the neocortex, and depletion of MAP2 (64%), SNAP-25 (34%), and α-synuclein (44%) proteins in the medial temporal lobes. These findings suggest that the t-SNARE complex deficit present in LBV may be associated with the presence of LB-related pathology and may explain the more profound cholinergic loss seen in these patients.
- Subjects :
- Male
Pathology
lcsh:Medicine
Neocortex
lcsh:Technology
chemistry.chemical_compound
tau
Phosphorylation
lcsh:Science
General Environmental Science
Aged, 80 and over
education.field_of_study
General Medicine
Temporal Lobe
medicine.anatomical_structure
alpha-Synuclein
Female
Alzheimer's disease
SNARE Proteins
dementia with Lewy bodies
Microtubule-Associated Proteins
Alzheimer’s disease
Braak staging
Research Article
Lewy Body Disease
medicine.medical_specialty
Article Subject
Population
Enzyme-Linked Immunosorbent Assay
tau Proteins
MAP2
t-SNARE complex
General Biochemistry, Genetics and Molecular Biology
α-synuclein
Alzheimer Disease
mental disorders
medicine
Dementia
Humans
education
Psychiatry
Aged
Alpha-synuclein
Lewy body
lcsh:T
business.industry
Dementia with Lewy bodies
lcsh:R
medicine.disease
chemistry
nervous system
lcsh:Q
Lewy Bodies
business
Synaptosomes
Subjects
Details
- ISSN :
- 1537744X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- TheScientificWorldJournal
- Accession number :
- edsair.doi.dedup.....852ee80c027207ea155fa82633b29731