Age-Related Distribution of Neuropathologic Changes in the Cerebral Cortex of Patients With Down's Syndrome

Hof, Patrick R.; Bouras, Constantin; Perl, Daniel P.; Sparks, D. Larry; Mehta, Nehal N.; Morrison, John H.

doi:10.1001/archneur.1995.00540280065020

Cited by 211 publications

(125 citation statements)

References 81 publications

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“…However, reports of further age-dependent increases in plasma Aβ in DS are variably reported as increased [38] or unchanged [8,55]. In CSF, there is an age dependent decrease in Aβ42 that may reflect increasing Aβ deposition in the brain [26].…”

Section: Discussionmentioning

confidence: 97%

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Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Nistor

Don

Parekh

et al. 2007

Neurobiology of Aging

104

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Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alphasecretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.

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Section: Discussionmentioning

confidence: 97%

“…Individuals with Down syndrome (DS) develop Alzheimer disease (AD) pathology in a progressive age-dependent manner [26,34,35,68] and as such, are at high risk for the development of dementia [29,33]. Clinical signs of dementia are more commonly observed when individuals are over 50 years of age [4,29,49,63].…”

Section: Introductionmentioning

confidence: 99%

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Nistor

Don

Parekh

et al. 2007

Neurobiology of Aging

104

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“…[79][80][81] Neuron loss is present in the locus coeruleus and basal forebrain. [82][83][84] The evidence from individuals carrying segmental Ts21 suggests the triplication of the amyloid beta precursor protein gene (APP) is necessary for Alzheimer-type neurodegeneration. [85][86][87][88][89] This is also consistent with a more recent report, in which a study of 30 people partially trisomic for Hsa21 provided evidence that an increased dose of APP is necessary for AD in DS.…”

Section: 71mentioning

confidence: 99%

Mouse-based genetic modeling and analysis of Down syndrome

Xing

Pao

et al. 2016

Br Med Bull

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“…In particular, a deficit of growth and maturation of the brain is consistently described, and patients develop a variable degree of cognitive impairment, usually leading to dementia after 50 years of age [17]. Neuropathologically, severe neuronal loss has been described in the hippocampal formation, neocortex and in subcortical areas [17]. The formation of NFT and amyloid deposits occurs prior to neuro nal loss.…”

Section: Amyotrophic Lateral Sclerosis/parkinsonism Dementia Complex mentioning

confidence: 99%

“…The hippocampal formation, including the entorhinal cortex, contains the highest number of NFT. Down's syndrome brain extracts contain significant amounts of insoluble tau [1,17].…”

Section: Amyotrophic Lateral Sclerosis/parkinsonism Dementia Complex mentioning

confidence: 99%

Tauopathies: A Distinct Class of Neurodegenerative Diseases

Ozansoy

Başak

2007

Balkan Journal of Medical Genetics

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Tauopathies: A Distinct Class of Neurodegenerative DiseasesNeurodegenerative diseases are characterized by neuronal loss and intraneuronal accumulation of fibrillary materials, of which, neurofibrillary tangles (NFT) are the most common. Neurofibrillary tangles also occur in normal aging and contain the hyperphosphorylated microtubule-associated protein tau. A detailed presentation is made of the molecular bases of Alzheimer's disease (AD), postencephalitic parkinsonism, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease, frontotemporal dementia (FTD), Down's syndrome, myotonic dystrophy (DM) and Niemann-Pick Type C (NPC) disease, which are considered to be common tauopathies. The unique human tau gene extends over 100 kb of the long arm of chromosome 17 and contains 16 exons. The human brain contains six tau isoforms that contain from 352 to 441 amino acids. To date, 34 pathogenic tau mutations have been described among 101 families affected by FTD with parkinsonism linked to chromosome 17 (FTDP-17). These mutations may involve alternative splicing of exon 10 that lead to changes in the proportion of 4-repeat- and 3-repeat-tau isoforms, or may modify tau interactions with microtubules. Tau aggregates differ in degree of phosphorylation and in content of tau isoforms. Five classes of tauopathies have been defined depending on the type of tau aggregates. The key event in tauopathies is the disorganization of the cytoskeleton, which is based on mutations/polymorphisms in the tau gene and lead to nerve cell degeneration. In this review, tauopathies as a distinct class of neurodegenerative diseases are discussed with emphasis on their molecular pathology and genetics.

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Age-Related Distribution of Neuropathologic Changes in the Cerebral Cortex of Patients With Down's Syndrome

Cited by 211 publications

References 81 publications

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Mouse-based genetic modeling and analysis of Down syndrome

Tauopathies: A Distinct Class of Neurodegenerative Diseases

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