{"doi":"10.33218/001c.77826","title":"Amyloid cascade hypothesis for Alzheimer’s disease. Does it work under physiological conditions?","abstract":"&lt;img src=” https://s3.amazonaws.com/production.scholastica/article/77826/large/prnano_942023_toc_figure.jpg?1686262046”&gt; Plaques in the brain consisting of proteins are a hallmark of diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such aggregates can be assembled spontaneously by specialized proteins such as amyloid beta (A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math>) proteins in the case of AD. Numerous in vitro studies made a foundation for the Amyloid Cascade Hypothesis (ACH), according to which the misfolding of proteins leads to their self-assembly into toxic oligomers along with the formation of amyloid fibrils assembled as plaques in the brain. Notably physiological concentration of A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math> proteins in the brain is in the low nanomolar concentration, so no spontaneous aggregation of A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math> protein occurs at such conditions, questioning the validity of the ACH model. However, recent studies revealed that surfaces could play a role as a catalyst of the aggregation process, so self-assembly of A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math> can be observed at physiologically low concentrations of A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math> proteins, although no spontaneous aggregation occurs in the bulk solution. The catalytic property of membrane surfaces towards A <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\"><mml:mi>β</mml:mi></mml:math> aggregation depends on the membrane composition. This finding suggests a number of novel ideas on molecular mechanisms of amyloid self-assembly, which lay a foundation for the development of treatments and preventions for AD, as discussed in this article.","journal":"Precision Nanomedicine","year":2023,"id":386303,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373682,"name":"Yuri L. Lyubchenko","orcid":"0000-0001-9721-8302","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:17:56.803401Z","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":[]}