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

Elizabeta B Mukaetova-Ladinska, John H Xuereb, Francisco Garcia-Sierra, Jenny Hurt, Hermann J Gertz, Richard Hills, Carol Brayne, Felicia A Huppert, Eugene S Paykel, Magnus A McGee, Ross Jakes, William G Honer, Charles R Harrington, Claude M Wischik, CC75C Collaboration Grp

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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 alpha-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 alpha-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.

Original languageEnglish
Pages (from-to)1463-1475
Number of pages13
JournalThe Scientific World Journal
Volume9
DOIs
Publication statusPublished - 16 Dec 2009

Cite this

Mukaetova-Ladinska, E. B., Xuereb, J. H., Garcia-Sierra, F., Hurt, J., Gertz, H. J., Hills, R., ... CC75C Collaboration Grp (2009). 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. The Scientific World Journal, 9, 1463-1475. https://doi.org/10.1100/tsw.2009.151

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. / Mukaetova-Ladinska, Elizabeta B; Xuereb, John H; Garcia-Sierra, Francisco; Hurt, Jenny; Gertz, Hermann J; Hills, Richard; Brayne, Carol; Huppert, Felicia A; Paykel, Eugene S; McGee, Magnus A; Jakes, Ross; Honer, William G; Harrington, Charles R; Wischik, Claude M; CC75C Collaboration Grp.

In: The Scientific World Journal, Vol. 9, 16.12.2009, p. 1463-1475.

Research output: Contribution to journalArticle

Mukaetova-Ladinska, EB, Xuereb, JH, Garcia-Sierra, F, Hurt, J, Gertz, HJ, Hills, R, Brayne, C, Huppert, FA, Paykel, ES, McGee, MA, Jakes, R, Honer, WG, Harrington, CR, Wischik, CM & CC75C Collaboration Grp 2009, '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', The Scientific World Journal, vol. 9, pp. 1463-1475. https://doi.org/10.1100/tsw.2009.151
Mukaetova-Ladinska, Elizabeta B ; Xuereb, John H ; Garcia-Sierra, Francisco ; Hurt, Jenny ; Gertz, Hermann J ; Hills, Richard ; Brayne, Carol ; Huppert, Felicia A ; Paykel, Eugene S ; McGee, Magnus A ; Jakes, Ross ; Honer, William G ; Harrington, Charles R ; Wischik, Claude M ; CC75C Collaboration Grp. / 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. In: The Scientific World Journal. 2009 ; Vol. 9. pp. 1463-1475.
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T1 - Lewy body variant of Alzheimer's disease

T2 - selective neocortical loss of t-SNARE proteins and loss of MAP2 and alpha-synuclein in medial temporal lobe

AU - Mukaetova-Ladinska, Elizabeta B

AU - Xuereb, John H

AU - Garcia-Sierra, Francisco

AU - Hurt, Jenny

AU - Gertz, Hermann J

AU - Hills, Richard

AU - Brayne, Carol

AU - Huppert, Felicia A

AU - Paykel, Eugene S

AU - McGee, Magnus A

AU - Jakes, Ross

AU - Honer, William G

AU - Harrington, Charles R

AU - Wischik, Claude M

AU - CC75C Collaboration Grp

PY - 2009/12/16

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N2 - 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 alpha-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 alpha-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.

AB - 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 alpha-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 alpha-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.

U2 - 10.1100/tsw.2009.151

DO - 10.1100/tsw.2009.151

M3 - Article

VL - 9

SP - 1463

EP - 1475

JO - The Scientific World Journal

JF - The Scientific World Journal

SN - 1537-744X

ER -