Variability of .BETA.-Amyloid Protein Deposited Lesions in Down's Syndrome Brains.

Ikeda, Shu Ichi; Tokuda, Takahiko; Yanagisawa, Nobuo; Kametani, Fuyuki; Ohshima, Toshio

doi:10.1620/tjem.174.189

Cited by 16 publications

(14 citation statements)

References 16 publications

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“…1A, B) and also contains post-translationally modi-fied Aβ [31]. CAA in DS may be associated with extensive cerebrovascular hemorrhages or stroke [7,22,42,60,62,69] in some studies but not in others [40,49]. In our autopsy studies, we find a significant number of microhemorrhages in the DS brain (Fig.…”

Section: Cerebrovascular Pathology In Down Syndromementioning

confidence: 68%

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Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome

Wilcock

Schmitt

Head

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40 years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of comorbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health.

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Section: Cerebrovascular Pathology In Down Syndromementioning

confidence: 68%

“…CAA can lead to micro- and macro-hemorrhages [99]. CAA is consistently observed in older individuals with DS over the age of 55 years old [7,40,49] (Fig. 1A, B) and also contains post-translationally modi-fied Aβ [31].…”

Section: Cerebrovascular Pathology In Down Syndromementioning

confidence: 99%

Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome

Wilcock

Schmitt

Head

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…CAA is consistently observed in older individuals with DS (>55 yrs - [84-86] and also contains post-translationally modified Aβ [67]. Interestingly, there are reports of CAA in DS that is associated with extensive hemorrhages [86-90] in some studies but not in others [84, 85]. Brain Aβ40 (typically associated with CAA – Figure 2B) rises exponentially with age in DS [36].…”

Section: Cerebrovascular Aβ Pathology In Dsmentioning

confidence: 99%

“…Aβ deposits and APP accumulation has been observed in the WM of the frontal cortex in DS [84, 147]. Ubiquitin positive punctuate deposits, that correspond to WM degeneration in the frontal cortex, increases after 21 years of age in DS [148].…”

Section: White Matter Degeneration In Dsmentioning

confidence: 99%

Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology

Head

Lott²,

Wilcock³

et al. 2015

CAR

216

210

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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 individuals 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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“…Individuals with Down's Syndrome (who are trisomic for chromosome 21, resulting in three copies of the bAPP gene instead of two) are at greater risk of AD. This overexpression of βAPP can lead to increased Aβ production and accumulation in brain decades earlier than in sporadic AD [15][16][17][18]. An exception which proves the rule is a case in which an individual with Down's Syndrome failed to develop AD, even though living for 78 years [19].…”

Section: Discussionmentioning

confidence: 99%

Emerging strategies for the treatment of Alzheimer’s disease at the Millennium

Emmerling¹,

Spiegel²,

Hall³

et al. 1999

Emerging Drugs

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It is estimated that by the year 2050 the number of cases of Alzheimer's disease (AD) will more than triple in the United States alone. As longevity increases, AD cases are expected to skyrocket from 4 -14 m. Globally, the numbers may reach 60 -80 m. Those expected to develop AD in the next century are presently in their 20s, 30s or 40s. Thus, steps must be taken to prevent this imminent epidemic, and the emotional and economic toll that it will exact on both patients and families. Numerous new strategies to treat AD have emerged in the last decade. This is the direct result of an increased understanding of the molecular pathology associated with the development of AD dementia, as well as the harvesting of results from case-control and cohort epidemiological studies. AD is no longer viewed solely as a disease of neurotransmitter deficits or amyloid deposition. Rather, it is a combination of events (amyloidosis, neurofibrillary pathology, inflammation, oxidative stress and cerebral vascular insufficiency) that conspire to produce this dementia. This avalanche of information reveals the complexity of the genetic and environmental contributors to AD. At the same time, these advances also delineate new avenues by which AD may be palliated, halted or averted. In the present review, we shall explore the emerging opportunities for the treatment and prevention of AD. 35 1999

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Variability of .BETA.-Amyloid Protein Deposited Lesions in Down's Syndrome Brains.

Cited by 16 publications

References 16 publications

Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome

Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome

Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology

Emerging strategies for the treatment of Alzheimer’s disease at the Millennium

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