Biechele, Gloria and Rauchmann, Boris-Stephan and Janowitz, Daniel and Buerger, Katharina and Franzmeier, Nicolai and Weidinger, Endy and Guersel, Selim and Schuster, Sebastian and Finze, Anika and Harris, Stefanie and Lindner, Simon and Albert, Nathalie L. and Wetzel, Christian H. and Rupprecht, Rainer and Rominger, Axel and Palleis, Carla and Katzdobler, Sabrina and Burow, Lena and Kurz, Carolin and Zaganjori, Mirlind and Trappmann, Lena-Katharina and Goldhardt, Oliver and Grimmer, Timo and Haeckert, Jan and Keeser, Daniel and Stoecklein, Sophia and Morenas-Rodriguez, Estrella and Bartenstein, Peter and Levin, Johannes and Hoeglinger, Guenter U. and Simons, Mikael and Perneczky, Robert and Brendel, Matthias (2024) Associations between sex, body mass index and the individual microglial response in Alzheimer's disease. JOURNAL OF NEUROINFLAMMATION, 21 (1): 30. ISSN , 1742-2094
Full text not available from this repository. (Request a copy)Abstract
Background and objectives18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer's disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between beta-amyloid-accumulation and microglial activation in AD.Methods49 patients with AD (29 females, all A beta-positive) and 15 A beta-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and beta-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional A beta-PET on TSPO-PET was used to determine the A beta-plaque-dependent microglial response (slope) and the A beta-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI).ResultsIn AD, females showed higher mean cortical TSPO-PET z-scores (0.91 +/- 0.49; males 0.30 +/- 0.75; p = 0.002), while A beta-PET z-scores were similar. The A beta-plaque-independent microglial response was stronger in females with AD (+ 0.37 +/- 0.38; males with AD - 0.33 +/- 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the A beta-plaque-dependent microglial response was not different between sexes. The A beta-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the A beta-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005).ConclusionWhile microglia response to fibrillar A beta is similar between sexes, women with AD show a stronger A beta-plaque-independent microglia response. This sex difference in A beta-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the A beta-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VASCULAR RISK-FACTORS; FALSE DISCOVERY RATE; TRANSLOCATOR PROTEIN; RADIOLIGAND BINDING; AMYLOID-BETA; PET; BRAIN; TAU; NEUROINFLAMMATION; ACTIVATION; Microglia; TSPO; Amyloid; Tau; Sex differences |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 08:34 |
| Last Modified: | 20 Aug 2025 08:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65543 |
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