{"doi":"10.1093/braincomms/fcac085","title":"Differentiating amyloid beta spread in autosomal dominant and sporadic Alzheimer’s disease","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.","journal":"Brain Communications","year":2022,"id":263099,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":920058,"name":"Jacob W Vogel","orcid":null,"position":1,"is_corresponding":false},{"id":457130,"name":"Thomas Funck","orcid":"0000-0002-8925-9830","position":2,"is_corresponding":false},{"id":73170,"name":"Vladimir Hachinski","orcid":"0000-0002-0487-734X","position":3,"is_corresponding":false},{"id":264345,"name":"Serge Gauthier","orcid":"0000-0003-4272-3330","position":4,"is_corresponding":false},{"id":301407,"name":"Jonathan Vöglein","orcid":"0000-0002-5965-838X","position":5,"is_corresponding":false},{"id":84330,"name":"Johannes Levin","orcid":"0000-0001-5092-4306","position":6,"is_corresponding":false},{"id":255192,"name":"Brian A. Gordon","orcid":"0000-0003-2109-2955","position":7,"is_corresponding":false},{"id":301875,"name":"Tammie L.S. Benzinger","orcid":"0000-0002-8114-0552","position":8,"is_corresponding":false},{"id":226047,"name":"Yasser Iturria‐Medina","orcid":"0000-0002-9345-0347","position":9,"is_corresponding":false},{"id":226050,"name":"Alan C. Evans","orcid":"0000-0003-3841-6098","position":10,"is_corresponding":false},{"id":498359,"name":"for the Dominantly Inherited Alzheimer Network","orcid":null,"position":11,"is_corresponding":false},{"id":243718,"name":"for the Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":12,"is_corresponding":false},{"id":226049,"name":"Elizabeth Levitis","orcid":"0000-0003-0905-6687","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:26:29.321923Z","pmid":"35602652","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}