Abstract
Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.
Keywords: Beta-amyloid, neurofibrillary tangles, neuroinflammation, oxidative damage, posttranslational modifications, senile plaques, trisomy 21, vascular pathology, white matter damage.
Current Alzheimer Research
Title:Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology
Volume: 13 Issue: 1
Author(s): Elizabeth Head, Ira T. Lott, Donna M. Wilcock and Cynthia A. Lemere
Affiliation:
Keywords: Beta-amyloid, neurofibrillary tangles, neuroinflammation, oxidative damage, posttranslational modifications, senile plaques, trisomy 21, vascular pathology, white matter damage.
Abstract: Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.
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Cite this article as:
Head Elizabeth, T. Lott Ira, M. Wilcock Donna and A. Lemere Cynthia, Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology, Current Alzheimer Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567205012666151020114607
DOI https://dx.doi.org/10.2174/1567205012666151020114607 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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