{"doi":"10.1093/cercor/bhaa184","title":"Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer’s Disease Continuum","abstract":"A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer's disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.5) diagnosed with AD dementia or mild cognitive impairment due to AD and available 11C-PiB (PIB), 18F-Flortaucipir (FTP),18F-FDG-PET, and 3T-MRI, and 31 amyloid-positive, cognitively normal participants (age 77.3 ± 6.5, no FDG-PET). W-score voxel-wise deviation maps were created and binarized for each imaging-modality (W > 1.64, P < 0.05) adjusting for age, sex, and total intracranial volume (sMRI-only) using amyloid-negative cognitively normal adults. For symptomatic patients, FDG-PET and atrophy W-maps were combined into neurodegeneration maps (ND). Aβ-pathology showed the greatest proportion of cortical gray matter suprathreshold voxels (spatial extent) for both symptomatic and asymptomatic participants (median 94-55%, respectively), followed by tau (79-11%) and neurodegeneration (41-3%). Amyloid > tau > neurodegeneration was the most frequent hierarchy for both groups (79-77%, respectively), followed by tau > amyloid > neurodegeneration (13-10%) and amyloid > neurodegeneration > tau (6-13%). For symptomatic participants, most abnormal voxels were PIB+/FTP+/ND- (median 35%), and the great majority of ND+ voxels (91%) colocalized with molecular pathology. Amyloid spatially exceeded tau and neurodegeneration, with individual heterogeneities. Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms.","journal":"Cerebral Cortex","year":2020,"id":65673,"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":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5295,"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":260103,"name":"Renaud La Joie","orcid":"0000-0003-2581-8100","position":1,"is_corresponding":false},{"id":300910,"name":"Lauren Edwards","orcid":"0000-0002-8434-9669","position":2,"is_corresponding":false},{"id":349416,"name":"Amelia Strom","orcid":null,"position":3,"is_corresponding":false},{"id":347737,"name":"Daniel R. Schonhaut","orcid":"0000-0001-8667-031X","position":4,"is_corresponding":false},{"id":230944,"name":"Rik Ossenkoppele","orcid":"0000-0003-1584-7477","position":5,"is_corresponding":false},{"id":275274,"name":"Julie Pham","orcid":"0000-0002-9621-3232","position":6,"is_corresponding":false},{"id":347738,"name":"Taylor J. Mellinger","orcid":"0000-0003-2319-631X","position":7,"is_corresponding":false},{"id":300909,"name":"Mustafa Janabi","orcid":"0000-0003-0134-0317","position":8,"is_corresponding":false},{"id":246340,"name":"Suzanne L. Baker","orcid":"0000-0003-0209-3127","position":9,"is_corresponding":false},{"id":347739,"name":"David N. Soleimani‐Meigooni","orcid":"0000-0003-4197-3039","position":10,"is_corresponding":false},{"id":230946,"name":"Howard J. Rosen","orcid":"0000-0001-9281-7402","position":11,"is_corresponding":false},{"id":58513,"name":"Bruce L. Miller","orcid":"0000-0002-2152-4220","position":12,"is_corresponding":false},{"id":51717,"name":"William J. Jagust","orcid":"0000-0002-4458-113X","position":13,"is_corresponding":false},{"id":230947,"name":"Gil D. Rabinovici","orcid":"0000-0002-3626-4265","position":14,"is_corresponding":false},{"id":275271,"name":"Leonardo Iaccarino","orcid":"0000-0003-0053-9519","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-18T21:13:43.728351Z","pmid":"32808011","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":[]}