{"doi":"10.1002/alz.12835","title":"Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of <i>APP</i> gene dose","abstract":"INTRODUCTION: Synaptic failure, a hallmark of Alzheimer's disease (AD), is correlated with reduced levels of synaptic proteins. Though people with Down syndrome (DS) are at markedly increased risk for AD (AD-DS), few studies have addressed synapse dysfunction. METHODS: Synaptic proteins were measured in the frontal cortex of DS, AD-DS, sporadic AD cases, and controls. The same proteins were examined in the Dp16 model of DS. RESULTS: A common subset of synaptic proteins were reduced in AD and AD-DS, but not in DS or a case of partial trisomy 21 lacking triplication of APP gene. Pointing to compromised synaptic function, the reductions in AD and AD-DS were correlated with reduced SNARE complexes. In Dp16 mice reductions in syntaxin 1A, SNAP25 and the SNARE complex recapitulated findings in AD-DS; reductions were impacted by both age and increased App gene dose. DISCUSSION: Synaptic phenotypes shared between AD-DS and AD point to shared pathogenetic mechanisms.","journal":"Alzheimer s & Dementia","year":2022,"id":254873,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8742,"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":902550,"name":"Xinxin Zuo","orcid":null,"position":1,"is_corresponding":false},{"id":647845,"name":"Ann Becker","orcid":"0000-0003-4892-9727","position":2,"is_corresponding":false},{"id":270466,"name":"Elizabeth Head","orcid":"0000-0003-1115-6396","position":3,"is_corresponding":false},{"id":226995,"name":"William C. Mobley","orcid":"0000-0002-6408-9548","position":4,"is_corresponding":false},{"id":711513,"name":"Xu‐Qiao Chen","orcid":"0000-0001-9799-7246","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T00:25:08.518416Z","pmid":"36370135","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":[]}