Associations between sex, body mass index and the individual microglial response in Alzheimer’s disease
Author:
Biechele Gloria1, Rauchmann Boris-Stephan1, Janowitz Daniel1, Buerger Katharina1, Franzmeier Nicolai1, Weidinger Endy1, Guersel Selim1, Schuster Sebastian1, Finze Anika1, Harris Stefanie1, Lindner Simon1, Albert Nathalie L.1, Wetzel Christian2, Rupprecht Rainer2, Rominger Axel3, Palleis Carla1, Katzdobler Sabrina1, Burow Lena1, Kurz Carolin1, Zaganjori Mirlind1, Trappmann Lena-Katharina1, Goldhardt Oliver4, Grimmer Timo4, Haeckert Jan5, Keeser Daniel1, Stoecklein Sophia1, Morenas-Rodriguez Estrella6, Bartenstein Peter1, Levin Johannes1, Höglinger Günter U.1, Simons Mikael1, Perneczky Robert1, Brendel Matthias1
Affiliation:
1. LMU University Hospital, LMU Munich 2. University of Regensburg 3. University of Bern 4. Technical University Munich, Klinikum rechts der Isar 5. University of Augsburg 6. University of Munich
Abstract
Abstract
Background and Objectives:
18-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 β-amyloid-accumulation and microglial activation in AD.
Methods:
49 patients with AD (29 females, all Aβ-positive) and 15 Aβ-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and β-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 Aβ-PET on TSPO-PET was used to determine the Aβ-plaque dependent microglial response (slope) and the Aβ-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).
Results:
In AD, females showed higher mean cortical TSPO-PET z-scores (0.91±0.49; males 0.30±0.75; p=0.002), while Aβ-PET z-scores were similar. The Aβ-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. Contrary, the Aβ-plaque dependent microglial response was not different between sexes. The Aβ-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 Aβ-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).
Conclusion:
While microglia response to fibrillar Aβ is similar between sexes, women with AD show a stronger Aβ-plaque independent microglia response. This sex difference in Aβ-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the Aβ-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.
Publisher
Research Square Platform LLC
|
|