{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:51Z","timestamp":1786977591040,"version":"build-2736575974"},"reference-count":106,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The precuneus (PreC; Brodmann area 7), a key hub within the default mode network (DMN) displays amyloid and tau\u2010containing neurofibrillary tangle (NFT) pathology during the onset of Alzheimer's disease (AD). PreC layer III projection neurons contain lysosomal hydrolase cathepsin D (CatD), a marker of neurons vulnerable to NFT pathology. Here we applied single population laser capture microdissection coupled with custom\u2010designed microarray profiling to determine the genetic signature of PreC CatD\u2010positive\u2010layer III neurons accrued from postmortem tissue obtained from the Rush Religious Orders Study (RROS) cases with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD. Expression profiling revealed significant differential expression of key transcripts in MCI and AD compared to NCI that underlie signaling defects, including dysregulation of genes within the endosomal\u2010lysosomal and autophagy pathways, cytoskeletal elements, AD\u2010related genes, ionotropic and metabotropic glutamate receptors, cholinergic enzymes and receptors, markers of monoamine neurotransmission as well as steroid\u2010related transcripts. Pervasive defects in both MCI and AD were found in select transcripts within these key gene ontology categories, underscoring the vulnerability of these corticocortical projection neurons during the onset and progression of dementia. Select PreC dysregulated genes detected via custom\u2010designed microarray analysis were validated using qPCR. In summary, expression profiling of PreC CatD \u2010positive layer III neurons revealed significant dysregulation of a mosaic of genes in MCI and AD that were not previously appreciated in terms of their indication of systems\u2010wide signaling defects in a key hub of the DMN.<\/jats:p>","DOI":"10.1002\/cne.24929","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T01:26:37Z","timestamp":1587605197000},"page":"2748-2766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expression profiling of precuneus layer\n                    <scp>III<\/scp>\n                    cathepsin D\u2010immunopositive pyramidal neurons in mild cognitive impairment and Alzheimer's disease: Evidence for neuronal signaling vulnerability"],"prefix":"10.1002","volume":"528","author":[{"given":"Bin","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Neurology Barrow 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New York USA"},{"name":"NYU Neuroscience Institute New York University School of Medicine  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Malek\u2010Ahmadi","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-7334","authenticated-orcid":false,"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Neurology Barrow Neurological Institute  Phoenix Arizona 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