Abstract | BACKGROUND: OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively. METHODS: Postmortem samples from temporal cortex (BA21) were measured for TGFβ2 using a Luminex-based platform, and correlated with scores for neuritic plaques, neurofibrillary tangles, α- synuclein pathology, dementia severity (as measured by annual decline of Mini-Mental State Examination scores) as well as soluble and total fractions of brain Aβ42. RESULTS: TGFβ2 was significantly increased in AD and DLB, but not in PDD. TGFβ2 also correlated with scores for neurofibrillary tangles, Lewy bodies (within the LBD group), dementia severity, and soluble Aβ42 concentration, but not with neuritic plaque scores, total Aβ42, or monomeric α- synuclein immunoreactivity. CONCLUSIONS: TGFβ2 is increased in the temporal cortex of AD and DLB, and its correlations with neuropathological and clinical markers of disease severity as well as with soluble Aβ42 load suggest a potential pathogenic role in mediating the neurotoxicity of non-fibrillar Aβ. Our study also indicates the potential utility of targeting TGFβ2 in pharmacotherapeutic approaches to AD and DLB.
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Authors | Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 56
Issue 1
Pg. 157-166
( 2017)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 27911312
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- Peptide Fragments
- Transforming Growth Factor beta2
- alpha-Synuclein
- amyloid beta-protein (1-42)
- tau Proteins
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Topics |
- Aged, 80 and over
- Alzheimer Disease
(pathology)
- Amyloid beta-Peptides
(metabolism)
- Analysis of Variance
- Diagnosis
- Female
- Humans
- Lewy Body Disease
(pathology)
- Male
- Neocortex
(metabolism)
- Peptide Fragments
(metabolism)
- Psychiatric Status Rating Scales
- Transforming Growth Factor beta2
(metabolism)
- alpha-Synuclein
(metabolism)
- tau Proteins
(metabolism)
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