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Basic Science and Pathogenesis.

Carolina Bidó Bello1, D Luke Fischer2, Agathe Vrillon1

  • 1Global Brain Health Institute, San Francisco, CA, USA.

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Summary
This summary is machine-generated.

Age-related co-pathologies like Alzheimer's disease (AD) neuropathologic changes and argyrophilic grain disease (AGD) are common in frontotemporal lobar degeneration (FTLD). These co-pathologies influence disease presentation and progression, underscoring the need for comprehensive assessment.

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Geriatric Medicine

Background:

  • Frontotemporal lobar degeneration (FTLD) comprises neurodegenerative diseases characterized by tau, TDP-43, or FET inclusions.
  • FTLD's younger age of onset has historically led to less research on age-related co-pathologies.
  • Co-pathologies significantly impact FTLD's clinical manifestations, diagnosis, and management.

Purpose of the Study:

  • To determine the frequency and types of co-pathologies within the FTLD spectrum.
  • To investigate the interplay between FTLD and common age-related neurodegenerative changes.
  • To understand the implications of co-pathology for clinical presentation and disease progression.

Main Methods:

  • Analysis of a large postmortem clinicopathological cohort of FTLD cases (2005-2024) from the Neurodegenerative Disease Brain Bank (NDBB) at UCSF.
  • Standardized neuropathological assessment of brains to identify primary FTLD pathologies and common age-related changes.
  • Inclusion of various FTLD subtypes (FTLD-TDP43 types A, B, C, unclassifiable; primary tauopathies like PSP, Pick's disease, CBD; FTLD-FET) and other neurodegenerative conditions.

Main Results:

  • Alzheimer's disease (AD) neuropathologic changes (66.6%) and argyrophilic grain disease (AGD, 33.5%) were the most frequent co-pathologies in 403 FTLD cases.
  • Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) showed higher frequencies of intermediate to advanced AD neuropathologic changes (ADNC).
  • Hippocampal sclerosis (HS) was observed in 8.2% of the cohort, notably frequent in FTLD-TDP43 type A (34.9%), FTLD-FET (33.3%), and Pick's disease (16%).

Conclusions:

  • Age-related co-pathologies, particularly AD neuropathologic changes and AGD, are prevalent in FTLD, albeit typically at a low burden.
  • The increased prevalence of ADNC in PSP and CBD suggests a potential contribution to their clinical presentation and progression.
  • Distinct vulnerabilities are highlighted by the frequency of HS in specific FTLD subtypes, emphasizing the need for comprehensive neuropathological evaluation for refined diagnosis and treatment strategies.