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Clinical Manifestations.

Nancy E Ortega1,2, Judy Pa3,4, Yonggand Shi5

  • 1Alzheimer's Disease Cooperative Study (ADCS), University of California San Diego, La Jolla, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Neuropsychiatric symptoms like apathy and depression are linked to specific brain tau pathology in individuals at risk for Autosomal Dominant Early Onset Alzheimer's disease (ADAD). This research highlights regional tau accumulation in relation to behavioral changes in ADAD.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Genetics

Background:

  • Investigating the link between neuropsychiatric symptoms and tau pathology in vivo.
  • Focusing on a cohort at risk for Autosomal Dominant Early Onset Alzheimer's disease (ADAD) due to PSEN1 and APP gene mutations.
  • Primarily including participants of Mexican ancestry.

Purpose of the Study:

  • To characterize the relationship between neuropsychiatric symptoms and in vivo tau pathology.
  • To examine regional associations of tau PET standard uptake value ratios (SUVrs) with Neuropsychiatric Inventory (NPI) scores.
  • To explore lateralization effects of these associations within each hemisphere.

Main Methods:

  • Utilized data from the Estudio de la Enfermedad de Alzheimer's en Jaliscienses (EEAJ) cohort.
  • Included participants with or at risk for PSEN1/APP mutations and sporadic late-onset Alzheimer's disease (LOAD).
  • Employed linear regression models adjusted for relevant demographic and genetic factors, controlling for false discovery rate.

Main Results:

  • Aberrant motor disturbances correlated with tau pathology in the entorhinal cortex and temporal pole.
  • Apathy showed a significant relationship with tau pathology in the left posterior cingulate cortex.
  • Depression was associated with tau in the superior frontal gyrus and left posterior cingulate cortex; irritability linked to left entorhinal cortex and right frontal pole.

Conclusions:

  • Neuropsychiatric symptoms are significantly associated with regional tau pathology in ADAD.
  • Findings underscore the connection between specific behavioral changes and localized tau accumulation in PSEN1/APP mutation carriers.
  • This study provides in vivo evidence linking neuropsychiatric manifestations to tau burden in early-onset Alzheimer's disease.