HAI Book 2025 - Flipbook - Page 391
Rani, Nisha
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Tau burden across Braak stages is associated with regionally
specific amyloid accumulation: insights from the BIOCARD cohort
Nisha Rani1, Kylie H Alm1, Daniel D. Callow1, Corinne Pettigrew2, Anja Soldan2, Michael Miller3,
Marilyn Albert2, Arnold Bakker1,2
1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, US
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, US
3
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, US
2
Alzheimer9s disease is characterized by accumulation of amyloid-´ (A´) plaques and tau tangles. A´ deposition
typically begins in neocortical regions years before onset of cognitive decline, while tau pathology spreads
systematically through select brain regions, typically described as Braak stages (I-VI). The impact of regional A´
on tau propagation remains a key research focus. We examined the associations between regional A´ and tau
burden measured by positron emission tomography (PET) in 192 participants without dementia (14 with mild
cognitive impairment [MCI]) in the BIOCARD cohort, of whom 52 (27%) were A´ positive. Amyloid status was
assessed using standardized uptake value ratios (SUVR) obtained from the medial orbitofrontal cortex (OFC),
lateral OFC, precuneus, posterior cingulate, anterior cingulate, parietal, temporal, and superior frontal regions
using 11C-PIB PET. Tau burden was quantified using 18F-MK6240 PET across 29 brain regions, assigned to each of
the Braak stages. Associations were examined with stepwise and hierarchical regressions, covarying for age, sex,
education, and ApoE4 status. In stepwise regression analyses for Braak stages (I-II), amyloid in the medial OFC
emerged as significantly associated with tau burden (β = 1.45, t = 4.75, p
