Basic Science and Pathogenesis.

Area of Science:

• Neuropathology
• Geriatric Medicine
• Neurodegenerative Diseases

Background:

• Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is a common cause of dementia in older adults.
• LATE-NC often co-occurs with other brain pathologies, complicating diagnosis and understanding.
• Investigating these co-occurrences is crucial for comprehending dementia etiology.

Purpose of the Study:

• To determine the frequency of various neuropathological lesions in individuals with LATE-NC.
• To examine the associations between LATE-NC and other neuropathological changes.
• To identify independent predictors of LATE-NC among co-existing pathologies.

Main Methods:

• Cross-sectional analysis of 1,434 Brazilian individuals from the Biobank for Aging Studies.
• Assessment of neuropathological data including LATE-NC, Braak stages (PD and NFT), CERAD, cerebral amyloid angiopathy, and hyaline arteriolosclerosis.
• Ordinal logistic regression and adjusted models to evaluate associations between LATE-NC and other lesions.

Main Results:

• Higher LATE-NC stages correlated with increased prevalence of most neuropathological lesions.
• LATE-NC was associated with higher frequencies of advanced Braak for NFT, Braak for PD, CERAD, cerebral amyloid angiopathy, and hyaline arteriolosclerosis.
• Adjusted analyses revealed a significant independent association only between LATE-NC and advanced Braak for PD stages (OR = 1.46).

Conclusions:

• Increased neuropathological lesion burden is associated with higher stages of LATE-NC.
• Lewy body pathology (Braak for PD) is the only neuropathological finding independently associated with LATE-NC.
• These findings highlight the complex interplay of pathologies in aging brains and dementia.