{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:24:42Z","timestamp":1791498282315,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health &amp; Medical Research Council","award":["NHMRC APP1163249"],"award-info":[{"award-number":["NHMRC APP1163249"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most neurodegenerative disorders take decades to develop, and their early detection is challenged by confounding non-pathological ageing processes. Therefore, the discovery of genes and molecular pathways in both peripheral and brain tissues that are highly predictive of disease evolution is necessary. To find genes that influence Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD) pathogenesis, human RNA-Seq transcriptomic data from Brodmann Area 9 (BA9) of the dorsolateral prefrontal cortex (DLPFC), whole blood (WB), and peripheral blood mononuclear cells (PBMC) were analysed using a combination of differential gene expression and a random forest-based machine learning algorithm. The results suggest that there is little overlap between PD and AD, and the AD brain signature is unique mainly compared to blood-based samples. Moreover, the AD-BA9 was characterised by changes in \u2018nervous system development\u2019 with Myocyte-specific enhancer factor 2C (Mef2C), encoding a transcription factor that induces microglia activation, a prominent feature. The peripheral AD transcriptome was associated with alterations in \u2018viral process\u2019, and FYN, which has been previously shown to link amyloid-beta and tau, was the prominent feature. However, in the absence of any overlap with the central transcriptome, it is unclear whether peripheral FYN levels reflect AD severity or progression. In PD, central and peripheral signatures are characterised by anomalies in \u2018exocytosis\u2019 and specific genes related to the SNARE complex, including Vesicle-associated membrane protein 2 (VAMP2), Syntaxin 1A (STX1A), and p21-activated kinase 1 (PAK1). This is consistent with our current understanding of the physiological role of alpha-synuclein and how alpha-synuclein oligomers compromise vesicle docking and neurotransmission. Overall, the results describe distinct disease-specific pathomechanisms, both within the brain and peripherally, for the two most common neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms23095200","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T14:49:38Z","timestamp":1651848578000},"page":"5200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Overlap between Central and Peripheral Transcriptomes in Parkinson\u2019s Disease but Not Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8461-7478","authenticated-orcid":false,"given":"Kosar","family":"Hooshmand","sequence":"first","affiliation":[{"name":"Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M.","family":"Halliday","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy S.","family":"Pineda","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg T.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-818X","authenticated-orcid":false,"given":"Boris","family":"Guennewig","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"639160","DOI":"10.3389\/fgene.2021.639160","article-title":"Exploring common therapeutic targets for neurodegenerative disorders using transcriptome study","volume":"12","author":"Dharshini","year":"2021","journal-title":"Front. 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