{"doi":"10.20944/preprints202501.2241.v1","title":"Associations of Environmental Exposure to Arsenic, Manganese, Lead and Cadmium on Alzheimer's Disease: A Review of Recent Evidence from Mechanistic Studies","abstract":"Numerous epidemiological studies indicate that populations exposed to environmental hazards such as heavy metals have a higher likelihood of developing Alzheimer's disease (AD) compared to those unexposed indicating a potential association between heavy metals exposure and Alzheimer's disease and related dementias (AD/ADRD). The aim of this review is to summarize contemporary mechanistic research exploring the associations of four important metals, Arsenic (As), Manganese (Mn), Lead (Pb), and Cadmium (Cd) with AD and possible pathways, processes, and molecular mechanisms on the basis of data from the most recent mechanistic studies. Primary research publications published during the last decade, were located using a search of the PubMed Database. A thorough literature search and final screening yielded 46 original research articles for this review. Of the 46 papers, 6 pertain to As, 9 to Mn, 21 to Pb, and 10 to Cd exposures and AD pathobiology. Environmental exposure to these heavy metals induce a wide range of pathological processes that intersect with well-known mechanisms of AD, such as oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation, autophagy dysfunction, and Tau hyperphosphorylation. While exposure to single metals shares some affected pathways, certain effects are unique to specific metals. For instance, Pb and Cd induce Blood-Brain Barrier (BBB) disruption, whereas As and Mn are associated with neuroinflammation, glutamate excitotoxicity, impaired Amyloid Precursor Protein processing, aberrant Nitric Oxide (NO) signaling, and cortical and synaptic dysfunction. Our reivew provides a deeper understanding of biological mechanisms showing how metals contribute to AD. Information regarding the potential metal-induced neurotoxicity regarding AD may help us develop effective therapeutic AD intervention and treatment.","journal":"Preprints.org","year":2025,"id":554850,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1374427,"name":"Md. Shiblur Rahaman","orcid":"0000-0002-9920-4809","position":1,"is_corresponding":false},{"id":1452728,"name":"Enrique Perez","orcid":"0000-0002-4939-4907","position":2,"is_corresponding":false},{"id":897461,"name":"Khalid Khan","orcid":"0000-0001-5513-0337","position":3,"is_corresponding":false},{"id":685321,"name":"Giasuddin Ahmed","orcid":"0000-0002-4730-2925","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:54:54.542303Z","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":[]}