In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
Abstract:
While the last two decades have seen important advances in the in vivo detection of Alzheimer’s disease (AD) pathology (i.e. β‐amyloid [Aβ] and Tau) using biomarkers (PET‐ and CSF‐based), the global use of these measures is quite limited due to high costs, insufficient availability and their invasive nature. Interest in blood‐based biomarkers for AD is growing due their greater accessibility and lower cost. We here aimed to investigate the relationship between ultrasensitive plasma‐based measures for AD and both cross‐sectional and longitudinal brain atrophy. Methods We evaluated cross‐sectional plasma samples for 307 participants (100 cognitively unimpaired (CU) elderly, and 207 cognitively impaired (CI; 101 with mild cognitive impairment (MCI) and 106 AD) from the European multicentre AddNeuroMed cohort. Single molecule array (Simoa) assays were performed for NfL, T‐tau, Aβ 42 , Aβ 40 and GFAp. P‐tau 181 was measured using an in‐house Simoa assay. Associations with longitudinal MRI (baseline, 3‐months, 12‐months) were performed using linear mixed models (adjusted for age, sex, education, APOE ε4 status, and interval between plasma and MRI). Three predefined MRI markers were selected: hippocampal volume (adjusted for intracranial volume), cortical thickness within a temporal meta‐ROI encompassing regions susceptible to AD (mean thickness in the bilateral entorhinal, inferior/middle temporal, and fusiform cortices) and whole‐brain cortical thickness. Results Cross‐sectionally, P‐tau 181 and whole‐brain cortical thickness were the only significant association for CU. In CI subjects, Aβ 42 /Aβ 40 and P‐tau 181 were significantly associated with hippocampal volume and temporal meta‐ROI/whole‐brain cortical thickness (Table 1). Longitudinally, increased baseline P‐tau 181 was associated with all three MRI measures in both CU and CI subjects (Table 1). Low Aβ 42 /Aβ 40 was also associated with all three MRI measures, though only in CI subjects. Further analyses will associate these plasma measures at the voxel level. Conclusion These results suggest that plasma‐based measurements of Aβ 42 /Aβ 40 and P‐tau 181 are associated with cross‐sectional atrophy levels and, more importantly, can predict brain atrophy over time, both in patients with AD and in CU elderly individuals. These findings add to a growing number of studies suggesting that these markers hold great promise, both as diagnostic tools as well as in research and clinical trials.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
