HAI Book 2025 - Flipbook - Page 167
Grothe, Michel
27
Tau-PET detects advanced primary age-related tauopathy mimicking
early-stage AD
Michel Grothe1, Alexis Moscoso2, Miguel Labrador-Espinosa2, Jesús Silva-Rodríguez1, Fiona
Heeman2, Alejandro Costoya-Sánchez3, Valle Camacho4, Martijn van Essen5, Ismini Mainta6,
Andrés Perissinotti7, Omar Rodríguez-Fonseca8, Federica Ribaldi9, Michael D. Devous, Sr.10,11,
Michael J. Pontecorvo10,11, Giovanni B. Frisoni9, Valentina Garibotto6, Michael Schöll2,5
1
Reina Sofia Alzheimer Center, CIEN Foundation, ISCIII, Madrid, ES
Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, SE
3
Nuclear Medicine Department, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de
Compostela, ES
4
Department of Nuclear Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona,
Barcelona, ES
5
Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, SE
6
Division of Nuclear Medicine, Geneva University Hospitals, Geneva, CH
7
Nuclear Medicine Department, Hospital Clínic Barcelona, Barcelona, ES
8
Nuclear Medicine Department, Lucus Augusti University Hospital, Lugo, ES
9
Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, CH
10
Avid Radiopharmaceuticals, Philadelphia, PA, US
11
Eli Lilly and Company, Indianapolis, IN, US
2
Background: Primary age-related tauopathy (PART) is typically limited to the medial temporal lobe, but in rare
cases it can show a more extensive distribution that associates with cognitive deficits mimicking Alzheimer9s
disease (AD), a condition that has been termed tangle-dominant disease. It remains unknown whether these
advanced forms of PART can be detected in-vivo using PET imaging.
Methods: We first studied the ante-mortem tau- and A´-PET imaging ([18F]flortaucipir, [18F]florbetapir), CSF
biomarker, and cognitive characteristics of an autopsy case with neuropathologically-confirmed tangle-dominant
disease (Braak V, Thal 0, CERAD 0). We then used a large in-vivo cohort of 2402 older individuals to screen A´PET-negative (8A-9;
2000
pg/ml) but positive for p-tau181 (>30 pg/ml)(Fig-1). Last clinical diagnosis before death was aMCI. In the in-vivo
cohort, only 3.6% (45/1264) of A- individuals were T+, but this proportion was significantly higher (9.9%) in
cognitively impaired individuals (aMCI/AD dementia). A-T+ showed a temporo-parietal tau-PET signal that was
spatially similar but less pronounced compared to A+T+ (Fig-2). CSF p-tau181 levels were significantly elevated in
A-T+ compared to A-T- (p=0.01), but A´42 levels did not differ (p=0.60). APOE-ε4 frequency in A-T+ (37%) was
markedly lower than for A+T+ (69%, p
