{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:04:25Z","timestamp":1753891465091,"version":"3.41.2"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>The basal forebrain cholinergic system relies on trophic support by nerve growth factor (NGF) to maintain its phenotype and function. In Alzheimer\u2019s disease (AD), basal forebrain cholinergic neurons (BFCNs) undergo progressive atrophy, suggesting a deficit in NGF trophic support. Within the central nervous system, NGF maturation and degradation are tightly regulated by an activity-dependent metabolic cascade. Here, we present a brief overview of the characteristics of Alzheimer\u2019s pathology in Down syndrome (DS) with an emphasis on this NGF metabolic pathway\u2019s disruption during the evolving Alzheimer\u2019s pathology. Such NGF dysmetabolism is well-established in Alzheimer\u2019s brains with advanced pathology and has been observed in mild cognitive impairment (MCI) and non-demented individuals with elevated brain amyloid levels. As individuals with DS inexorably develop AD, we then review findings that support the existence of a similar NGF dysmetabolism in DS coinciding with atrophy of the basal forebrain cholinergic system. Lastly, we discuss the potential of NGF-related biomarkers as indicators of an evolving Alzheimer\u2019s pathology in DS.<\/jats:p>","DOI":"10.3389\/fnagi.2021.719507","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T06:00:09Z","timestamp":1628488809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nerve Growth Factor Compromise in Down Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Sonia","family":"Do Carmo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Kannel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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