Biomarkers.

Area of Science:

• Neuroscience
• Neuropathology
• Biomarkers

Background:

• Late-onset Alzheimer's Disease (AD) involves β-amyloid (Aβ) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC).
• The relationship between Aβ and LATE-NC in Down syndrome (DS), a population predisposed to early AD, is unexamined.
• This study compares Aβ deposition and neuropathologic changes in DS and late-onset AD cohorts.

Purpose of the Study:

• To investigate the association between antemortem Aβ deposition and postmortem neuropathologic changes in individuals with Down syndrome (DS).
• To compare these associations with those observed in a cohort with late-onset Alzheimer's Disease (AD).

Main Methods:

• Utilized data from the Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) and Pittsburgh Alzheimer's Disease Research Center (ADRC).
• Assessed Aβ PET scans (centiloids), postmortem MRI volumes (amygdala, hippocampus), and detailed histopathology.
• Employed statistical analyses including t-tests, linear regressions, and ANCOVA to compare cohorts and examine associations.

Main Results:

• The DS cohort had similar Aβ burden but younger age at diagnosis, smaller brain volumes, and more advanced CERAD scores compared to the AD cohort.
• Antemortem Aβ burden did not correlate with postmortem amygdala or hippocampal volumes in either cohort.
• In DS, higher Aβ burden was linked to advanced LATE-NC stage, while in the AD cohort, Aβ burden correlated with amyloid plaques and neurofibrillary tangles.

Conclusions:

• In Down syndrome, antemortem Aβ PET burden is associated with advanced LATE-NC stage, not postmortem brain volumes.
• In the late-onset AD cohort, Aβ burden correlates with established markers of AD pathology: amyloid plaques and neurofibrillary tangles.