TY  - JOUR
AU  - Bischof, Gérard N.
AU  - Jaeger, Elena
AU  - Giehl, Kathrin
AU  - Jessen, Frank
AU  - Onur, Oezguer A.
AU  - O'Bryant, Sid
AU  - Kara, Esra
AU  - Weiss, Peter H.
AU  - Drzezga, Alexander
TI  - Cortical Tau Aggregation Patterns Associated With Apraxia in Patients With Alzheimer Disease
JO  - Neurology
VL  - 103
IS  - 12
SN  - 0028-3878
CY  - Philadelphia, Pa.
PB  - Wolters Kluwer
M1  - FZJ-2025-00566
SP  - e210062
PY  - 2024
N1  - A. Drzezga, G.N. Bischof, E. Jaeger, and P.H. Weiss are fundedby the Deutsche Forschungsgemeinschaft - Project-ID431549029 - SFB 1451. G.N. Bischof received funding fromAlzheimer Forschung Initiative e.V., Germany (AFI K1707).In addition, this study was supported by the German ResearchFoundation (DFG, DR 445/9-1). Precursor for the synthesisof the tracer [18F]PI-2620 was kindly provided by Life Molecularimaging. The [18F]PI-2620 control sample was kindlyprovided by SidO’Bryant and were taken from the HABS-HDdatabase (apps.unthsc.edu/itr/studies/habs). Researchreported on this publication was supported by the NationalInstitute on Aging of the NIH under Award NumbersR01AG054073, R01AG058533, P41EB015922, andU19AG078109. The content is solely the responsibility of theauthors and does not necessarily represent the official views ofthe NIH.
AB  - Background and objectives: Apraxia is a frequently observed symptom in Alzheimer disease (AD), but the causal pathomechanism underlying this dysfunction is not well understood. Previous studies have demonstrated associations between various cognitive dysfunctions in AD and cortical tau deposition in specific brain areas, suggesting a causal relationship. Thus, we hypothesized that specific regional patterns of tau pathology in praxis-related brain regions may be associated with apraxic deficits in AD. For this purpose, we performed PET imaging with the second-generation tau-PET tracer [18F]PI-2620 in a well-defined group of patients with AD (N = 33) who had been systematically assessed for apraxia.Methods: Patients with a biomarker-confirmed diagnosis of AD were recruited in addition to a sample of cognitively unimpaired (CU1) control participants. Both groups underwent apraxia assessments with the Dementia Apraxia Screening Test. In addition, PET imaging with [18F]PI-2620 was performed to assess tau pathology in the patients with AD. To specifically investigate the association of apraxia severity with regional tau pathology, we compared the PET data from this group with an independent sample of amyloid-negative cognitively intact participants (CU2) by generation of z-score deviation maps and submitted these maps to a voxel-based multiple regression analysis.Results: A total of 120 participants (39% female) with a mean age of 67.9 (9.2) years were included in the study (AD = 33; CU1; N = 33; CU2; N = 54). We identified a significant correlation between circumscribed clusters of tau aggregation in praxis-related brain regions (including parietal (angular gyrus), temporal, and occipital regions) and severity of apraxia in patients with AD. By contrast, no significant correlations between tau tracer uptake in primary motor cortex or subcortical brain regions and apraxia were observed.Discussion: These results suggest that tau deposition in specific cortical praxis-related brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance in AD. The awareness of this relationship could further refine a differentiated individual diagnostic characterization and classification of patients with AD.
LB  - PUB:(DE-HGF)16
C6  - 39626130
UR  - <Go to ISI:>//WOS:001370437800001
DO  - DOI:10.1212/WNL.0000000000210062
UR  - https://juser.fz-juelich.de/record/1037233
ER  -