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Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease. | LitMetric

AI Article Synopsis

  • The study investigates how Alzheimer's disease and alpha-synucleinopathy (linked to Lewy body dementia) coexist and affect dementia symptoms, focusing on the maturation of tau protein tangles in the brain.
  • Using digital histology, researchers compared tau pathology in individuals with pure Alzheimer's, pure alpha-synucleinopathy, and mixed pathology, finding that tau levels were lower in the mixed group.
  • Results indicate that mature tau is more strongly associated with beta-amyloid rather than alpha-synuclein and suggests that the maturation of tau may influence dementia symptoms, particularly in cases of mixed pathology.

Article Abstract

Objective: Alzheimer's disease neuropathologic change and alpha-synucleinopathy commonly co-exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta-amyloid compared to alpha-synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia.

Methods: We used digital histology to measure percent area-occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha-synucleinopathy, and a co-pathology group with both Alzheimer's and alpha-synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features.

Results: There were lower levels of tau pathology (β = 1.86-2.96, p < 0.001) across all tau antibodies in the co-pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha-synucleinopathy, higher alpha-synuclein was associated with greater early tau (AT8 β = 1.37, p < 0.001; MC1 β = 1.2, p < 0.001) but not mature tau (TauC3 p = 0.18), whereas mature tau was associated with beta-amyloid (β = 0.21, p = 0.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies.

Interpretation: Mature tau may be more closely related to beta-amyloidosis than alpha-synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy-Alzheimer's pathology.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963284PMC
http://dx.doi.org/10.1002/acn3.51988DOI Listing

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