{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:09:43Z","timestamp":1777468183197,"version":"3.51.4"},"reference-count":11,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Brain and Neuroscience Advances"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Although neuritic plaques \u2013 comprised of aggregated fibrils of the misfolded protein, amyloid \u03b2 (A\u03b2) \u2013 have formed a central focus of Alzheimer\u2019s disease (AD) research for decades, it is now well understood that plaque burden alone is a poor correlate of cognitive decline. This is highlighted especially when compared against other neuropathological hallmarks, such as synapse loss (the strongest correlate) and hyperphosphorylated protein tau. However, it is known that Familial AD arises due to autosomal dominant mutations directly influencing the generation of A\u03b2, suggesting that A\u03b2 pathology may play a key upstream role in the disease. Such contrasting lines of evidence have thus raised questions as to why some aged individuals with high plaque burden develop AD while others remain cognitively healthy. In their recent study, published in Analytical Chemistry (June 2024), Enzlein and colleagues aimed to investigate whether differences in the molecular composition of plaques between individuals with sporadic Alzheimer\u2019s disease (N\u2009=\u20099) versus age-matched amyloid positive but cognitively unaffected controls (N\u2009=\u20098) could go towards explaining this outstanding question in the field. Using novel methods integrating mass spectrometry imaging with machine learning feature extraction, the authors compared peptide and lipid profiles to a resolving limit of 400\u2009\u03bcm2 for &gt;5000 individual plaques. In doing so, a distinct peptide signature was identified in sporadic Alzheimer\u2019s disease plaques that was characterised by strongly increased aggregation of the short amyloid \u03b2 isoform, A\u03b21-38 coupled with a lesser co-aggregation of pyroglutamate-modified A\u03b23-42pE. Sporadic Alzheimer\u2019s disease plaques also demonstrated a robust lipid signature denoted by an increased presence of cell membrane components, GM1 and GM2 gangliosides. Here, we review this work; aiming to place these findings within the context of existing literature and with a view to discussing their importance in developing our current knowledge of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1177\/23982128241280001","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T09:38:43Z","timestamp":1726825123000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Not all plaques are created equal: Uncovering a unique molecular signature in Alzheimer\u2019s disease"],"prefix":"10.1177","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3903-6361","authenticated-orcid":false,"given":"Kristjan","family":"Holt","sequence":"first","affiliation":[{"name":"Translational Neuroscience PhD Programme, The University of Edinburgh, Edinburgh, UK"},{"name":"Centre for Discovery Brain Sciences and UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-1148","authenticated-orcid":false,"given":"Emily","family":"Payne","sequence":"additional","affiliation":[{"name":"Translational Neuroscience PhD Programme, The University of Edinburgh, Edinburgh, UK"},{"name":"Centre for Discovery Brain Sciences and UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-0598","authenticated-orcid":false,"given":"Tara L.","family":"Spires-Jones","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences and UK Dementia Research Institute, The University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"bibr1-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13355"},{"key":"bibr2-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04733"},{"key":"bibr3-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013228"},{"key":"bibr4-23982128241280001","author":"Hardy JA","year":"1992","journal-title":"Science"},{"key":"bibr5-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.027"},{"key":"bibr6-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad159"},{"key":"bibr7-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0132-6"},{"key":"bibr8-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14593"},{"key":"bibr9-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70228-4"},{"key":"bibr10-23982128241280001","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-131373"},{"key":"bibr11-23982128241280001","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.004"}],"container-title":["Brain and Neuroscience Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/23982128241280001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/23982128241280001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/23982128241280001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:33:03Z","timestamp":1777383183000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/23982128241280001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":11,"alternative-id":["10.1177\/23982128241280001"],"URL":"https:\/\/doi.org\/10.1177\/23982128241280001","relation":{},"ISSN":["2398-2128","2398-2128"],"issn-type":[{"value":"2398-2128","type":"print"},{"value":"2398-2128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"article-number":"23982128241280001"}}