Differentiating amyloid beta spread in autosomal dominant and sporadic Alzheimer's disease. Issue 3 (13th April 2022)

• Record Type: Journal Article
• Authors: Levitis, Elizabeth; Vogel, Jacob W; Funck, Thomas; Hachinski, Vladimir; Gauthier, Serge; Vöglein, Jonathan; Levin, Johannes; Gordon, Brian A; Benzinger, Tammie; Iturria-Medina, Yasser; Evans, Alan C
• Is Part Of: Brain communications. Volume 4:Issue 3(2022)
• Publication Date: 2022-04-13
• Subjects: amyloid beta -- Alzheimer's disease -- diffusion models -- brain networks; 616
• DOI: 10.1093/braincomms/fcac085
• Languages: English
• ISSNs: 2632-1297

Abstract

Abstract: Amyloid-beta deposition is one of the hallmark pathologies in both sporadic Alzheimer's disease and autosomal-dominant Alzheimer's disease, the latter of which is caused by mutations in genes involved in amyloid-beta processing. Despite amyloid-beta deposition being a centrepiece to both sporadic Alzheimer's disease and autosomal-dominant Alzheimer's disease, some differences between these Alzheimer's disease subtypes have been observed with respect to the spatial pattern of amyloid-beta. Previous work has shown that the spatial pattern of amyloid-beta in individuals spanning the sporadic Alzheimer's disease spectrum can be reproduced with high accuracy using an epidemic spreading model which simulates the diffusion of amyloid-beta across neuronal connections and is constrained by individual rates of amyloid-beta production and clearance. However, it has not been investigated whether amyloid-beta deposition in the rarer autosomal-dominant Alzheimer's disease can be modelled in the same way, and if so, how congruent the spreading patterns of amyloid-beta across sporadic Alzheimer's disease and autosomal-dominant Alzheimer's disease are. We leverage the epidemic spreading model as a data-driven approach to probe individual-level variation in the spreading patterns of amyloid-beta across three different large-scale imaging datasets (2 sporadic Alzheimer's disease, 1 autosomal-dominant Alzheimer's disease). We applied the epidemic spreading model separately to the Alzheimer's Disease Neuroimaging initiative ( n = 737), the Open Access Series of Imaging Studies ( n = 510) and the Dominantly Inherited Alzheimer's Network ( n = 249), the latter two of which were processed using an identical pipeline. We assessed inter- and intra-individual model performance in each dataset separately and further identified the most likely subject-specific epicentre of amyloid-beta spread. Using epicentres defined in previous work in sporadic Alzheimer's disease, the epidemic spreading model provided moderate prediction of the regional pattern of amyloid-beta deposition across all three datasets. We further find that, whilst the most likely epicentre for most amyloid-beta–positive subjects overlaps with the default mode network, 13% of autosomal-dominant Alzheimer's disease individuals were best characterized by a striatal origin of amyloid-beta spread. These subjects were also distinguished by being younger than autosomal-dominant Alzheimer's disease subjects with a default mode network amyloid-beta origin, despite having a similar estimated age of symptom onset. Together, our results suggest that most autosomal-dominant Alzheimer's disease patients express amyloid-beta spreading patterns similar to those of sporadic Alzheimer's disease, but that there may be a subset of autosomal-dominant Alzheimer's disease patients with a separate, striatal phenotype. Abstract : Using an epidemic spreading model and three independent datasets, Levitis et al. show evidence for transneuronal amyloid spread in sporadic and autosomal-dominant Alzheimer's disease. Whilst most autosomal dominant patients showed a similar spread pattern to sporadic Alzheimer's disease, a separate phenotype with younger onset and a striatal phenotype emerged. Graphical Abstract: Graphical Abstract