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Cristiano Aguzzoli1,2,3, Guilherme Povala4, Pamela C L Ferreira4

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Summary
This summary is machine-generated.

Tau pathology is linked to motor disturbances in Alzheimer's disease (AD), but not irritability. This research clarifies tau's role in neuropsychiatric symptoms (NPS) across the AD continuum, guiding future AD treatments.

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomarkers

Background:

  • Previous research indicates a link between tau pathology and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD).
  • The specific influence of tau on individual NPS domains throughout the AD continuum remains incompletely understood.
  • This study investigates the association between tau biomarkers and specific NPS domains in individuals across the AD spectrum.

Purpose of the Study:

  • To investigate the association between tau pathology and specific neuropsychiatric symptom (NPS) domains in the Alzheimer's disease (AD) continuum.
  • To test the hypothesis that tau pathology disproportionately affects hyperactive and psychotic symptoms compared to other NPS domains.
  • To differentiate the impact of tau on various NPS domains, including motor disturbances and irritability.

Main Methods:

  • Assessed 385 individuals (cognitively unimpaired, MCI, AD dementia) using the Neuropsychiatry Inventory Questionnaire (NPI-Q) and tau-PET imaging ([18F]MK6240).
  • Utilized voxel-wise and censored regression models, controlling for age, sex, and cognitive status, to analyze the association between NPS domains and tau SUVR.
  • Employed a leave-one-out approach to identify key NPS domains contributing to the observed associations with tau pathology.

Main Results:

  • Individuals with cognitive impairment showed higher NPI-Q scores and tau-PET SUVR compared to cognitively unimpaired individuals.
  • Tau-PET SUVR was significantly associated with NPS, particularly in fronto-parietal regions, with motor disturbances being the strongest contributor across all Braak stages.
  • Irritability showed a negative association, suggesting tau pathology is not associated with its development, while motor disturbances are highly associated.

Conclusions:

  • Tau pathology is associated with the development of motor disturbances but not irritability across the Alzheimer's disease continuum.
  • These findings highlight the specific role of tau in certain NPS, differentiating its impact on motor symptoms versus irritability.
  • The results support the development of targeted therapeutics for mitigating motor disturbances and irritability in AD patients.