Restricted accessResearch articleFirst published online 2017-1-12
Increased Transforming Growth Factor β2 in the Neocortex of Alzheimer’s Disease and Dementia with Lewy Bodies is Correlated with Disease Severity and Soluble Aβ 42 Load
Background: Of the three transforming growth factor (TGF)-β isoforms known,
TGFβ1 deficits have been widely reported in Alzheimer’s disease (AD) and studied as a
potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to
mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body
dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden.
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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