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Clinical Manifestations.

Anqi Li1, Lizhi Guo2, Xin Zhou1,3

  • 1Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

High loneliness is linked to increased tau pathology in Alzheimer's disease (AD), particularly in individuals with cognitive impairment or amyloid-β (Aβ) presence. This highlights the connection between psychological state and AD progression.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Gerontology

Background:

  • Loneliness is linked to increased dementia risk and Alzheimer's disease (AD) pathology severity.
  • Amyloid-β (Aβ) and tau accumulation are key features of early-stage AD pathology.
  • The amygdala, a brain region associated with loneliness, plays a role in emotional processing.

Purpose of the Study:

  • To investigate the association between loneliness and the progression of AD pathology.
  • To examine the specific impact of loneliness on tau pathology in the amygdala.
  • To explore how loneliness relates to biomarkers of AD, including plasma phosphorylated tau (p-Tau) and Aβ deposition.

Main Methods:

  • 274 cognitively unimpaired (CU) and 99 cognitively impaired (CI) participants were assessed for loneliness, isolation, and depression.
  • Plasma p-Tau217, Aβ PET, and tau PET scans were utilized to measure AD pathology.
  • Linear regression models analyzed the relationship between loneliness and AD biomarkers, adjusting for relevant covariates.

Main Results:

  • Loneliness levels increased with the onset of AD pathology, particularly tau pathology (tau PET and plasma p-Tau217).
  • Loneliness positively correlated with plasma p-Tau217 and amygdala tau deposition, especially in CI and Aβ-positive individuals.
  • Amygdala volume showed a negative correlation with loneliness in the Aβ-positive group.

Conclusions:

  • Elevated loneliness is associated with increased tau pathology in AD, especially in those with cognitive impairment or Aβ pathology.
  • These findings suggest a significant link between loneliness and tau aggregation in AD.
  • Understanding the impact of neuropsychiatric states like loneliness on AD pathology can offer novel therapeutic insights.