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Basic Science and Pathogenesis.

Davis C Woodworth1, Jerry Jierui Lou1, William H Yong1

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Summary
This summary is machine-generated.

Hippocampal sclerosis of aging (HS-A) is strongly linked to limbic-predominant age-related TDP-43 encephalopathy (LATE-NC). Vascular changes also associate with HS-A, independent of LATE-NC.

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Area of Science:

  • Neuropathology
  • Geriatric Medicine
  • Neurodegenerative Diseases

Background:

  • Hippocampal sclerosis of aging (HS-A) affects up to 20% of elderly individuals with dementia, characterized by neuronal loss and gliosis in the hippocampus.
  • HS-A is strongly associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), but its relationship with other neuropathologic changes (NCs) requires clarification.
  • Accounting for LATE-NC is crucial when investigating associations between other NCs and HS-A due to their strong relationship.

Purpose of the Study:

  • To investigate the associations between common neuropathologic changes (NCs) and hippocampal sclerosis of aging (HS-A).
  • To determine if these associations persist after accounting for limbic-predominant age-related TDP-43 encephalopathy (LATE-NC).

Main Methods:

  • Utilized data from the National Alzheimer's Coordinating Center (NACC), excluding frontotemporal lobar degeneration (FTLD).
  • Examined associations of Alzheimer's disease neuropathologic change (ADNC), Lewy bodies (LB), and cerebrovascular pathologies with HS-A, with and without controlling for LATE-NC stage.
  • Employed Bayesian multilevel logistic regression models, reporting odds ratios (OR) and 95% credibility intervals (CI).

Main Results:

  • Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) showed a strong association with hippocampal sclerosis of aging (HS-A) (average OR=3.7).
  • Alzheimer's disease neuropathologic change (ADNC) association with HS-A diminished after accounting for LATE-NC (OR=1.11).
  • Cerebrovascular changes, including atherosclerosis, arteriolosclerosis, and white matter rarefaction (WMR), were associated with HS-A both before and after accounting for LATE-NC (ORs~1.5).

Conclusions:

  • Hippocampal sclerosis of aging (HS-A) is strongly and uniquely related to limbic-predominant age-related TDP-43 encephalopathy (LATE-NC).
  • Vascular neuropathologic changes (arteriolosclerosis, atherosclerosis, and WMR) are independently associated with HS-A.
  • These findings highlight the distinct roles of LATE-NC and vascular factors in the development of HS-A.