{"doi":"10.1101/2020.05.18.103226","title":"Time between milestone events in the Alzheimer’s disease amyloid cascade","abstract":"Abstract Objective Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer’s disease. Methods In a cohort of 336 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Results Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 11-12 years before Aβ-positivity. Temporoparietal tau PET showed increases 4-5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 7-9 years before Aβ-positivity. Conclusions Increases in tau and cognitive dysfunction occur years before the presence of significant Aβ. Explicit estimates of the time for these events provide a clearer picture of the time course of the amyloid cascade and identify potential windows for specific treatments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122762,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9341,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51716,"name":"Michael Donohue","orcid":"0000-0001-6026-2238","position":1,"is_corresponding":false},{"id":260106,"name":"David Berron","orcid":"0000-0003-1558-1883","position":2,"is_corresponding":false},{"id":65584,"name":"Oskar Hansson","orcid":"0000-0001-8467-7286","position":3,"is_corresponding":false},{"id":230942,"name":"Niklas Mattsson","orcid":"0000-0002-8885-7724","position":4,"is_corresponding":false},{"id":230945,"name":"Philip S. Insel","orcid":"0000-0002-6270-5490","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","pmid":null,"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":[]}