scholarly journals Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: overlaps in Down's syndrome and Alzheimer's disease brain

2014 ◽  
Vol 463 (2) ◽  
pp. 177-189 ◽  
Author(s):  
D. Allan Butterfield ◽  
Fabio Di Domenico ◽  
Aaron M. Swomley ◽  
Elizabeth Head ◽  
Marzia Perluigi
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Protein Function ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Post Translational Modifications ◽  
Redox Proteomics ◽  
Age Related

Accumulation of oxidative damage is a common feature of neurodegeneration that, together with mitochondrial dysfunction, point to the fact that reactive oxygen species are major contributors to loss of neuronal homoeostasis and cell death. Among several targets of oxidative stress, free-radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases. In the majority of cases, oxidative-stress-mediated post-translational modifications cause non-reversible modifications of protein structure that consistently lead to impaired function. Redox proteomics methods are powerful tools to unravel the complexity of neurodegeneration, by identifying brain proteins with oxidative post-translational modifications that are detrimental for protein function. The present review discusses the current literature showing evidence of impaired pathways linked to oxidative stress possibly involved in the neurodegenerative process leading to the development of Alzheimer-like dementia. In particular, we focus attention on dysregulated pathways that underlie neurodegeneration in both aging adults with DS (Down's syndrome) and AD (Alzheimer's disease). Since AD pathology is age-dependent in DS and shows similarities with AD, identification of common oxidized proteins by redox proteomics in both DS and AD can improve our understanding of the overlapping mechanisms that lead from normal aging to development of AD. The most relevant proteomics findings highlight that disturbance of protein homoeostasis and energy production are central mechanisms of neurodegeneration and overlap in aging DS and AD. Protein oxidation affects crucial intracellular functions and may be considered a ‘leitmotif’ of degenerating neurons. Therapeutic strategies aimed at preventing/reducing multiple components of processes leading to accumulation of oxidative damage will be critical in future studies.

Population-based study of the prevalence and presentation of dementia in adults with Down's syndrome

1998 ◽  
Vol 172 (6) ◽  
pp. 493-498 ◽  
Author(s):  
Anthony J. Holland ◽  
Johnny Hon ◽  
Felicia A. Huppert ◽  
Fran Stevens ◽  
Peter Watson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
The Elderly ◽  
Population Based ◽  
Prevalence Rates ◽  
Population Based Study ◽  
Age Related ◽  
Living Skills

BackgroundThe reported prevalence rates of dementia in people with Down's syndrome have varied considerably across studies. The aim of this study was to investigate the extent of clinical change with age using an established diagnostic instrument in an unbiased, population-based sample of older people with Down's syndrome.MethodChanges in memory, personality, general mental functioning and daily living skills were assessed using a modified version of the informant interview of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX).ResultsAge-specific prevalence rates of dementia varied according to the diagnostic criteria used. Using CAMDEX criteria for Alzheimer's disease, prevalence rates increased from 3.4 to 10.3 to 40% in the 30–39, 40–49 and 50–59 age group, respectively.ConclusionsOverall, the age-related pattern of presentation and dementia diagnoses differs from that seen in the general elderly population. However, age-specific prevalence rates of Alzheimer's disease were similar but 30–40 years earlier in life.

A four year prospective study of age-related cognitive change in adults with Down's syndrome

1998 ◽  
Vol 28 (6) ◽  
pp. 1365-1377 ◽  
Author(s):  
C. OLIVER ◽  
L. CRAYTON ◽  
A. HOLLAND ◽  
S. HALL ◽  
J. BRADBURY
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Cognitive Change ◽  
Individual Growth ◽  
Cognitive Deterioration ◽  
Age Related ◽  
The Individual

Background. While neuropathological studies indicate a high risk for Alzheimer's disease in adults with Down's syndrome, neuropsychological studies suggest a lower prevalence of dementia. In this study, cognitive deterioration in adults with Down's syndrome was examined prospectively over 4 years to establish rates and profiles of cognitive deterioration.Methods. Fifty-seven people with Down's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months. Assessments of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed. These included tests of learning, memory, orientation, agnosia, apraxia and aphasia. The individual growth trajectory methodology was used to analyse change over time.Results. Severe cognitive deterioration, such as acquired, apraxia and agnosia, was evident in 28·3% of those aged over 30 and a higher prevalence of these impairments was associated with older age. The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment. Additionally, deterioration in memory, learning and orientation preceded the acquisition of aphasia, agnosia and apraxia.Conclusions. The prevalence of cognitive impairments consistent with the presence of Alzheimer's disease is lower than that suggested by neuropathological studies. The pattern of the acquisition of cognitive impairments in adults with Down's syndrome is similar to that seen in individuals with Alzheimer's disease who do not have Down's syndrome.

scholarly journals Age-Related Neuronal Deterioration Specifically Within the Dorsal CA1 Region of the Hippocampus in a Mouse Model of Late Onset Alzheimer’s Disease

2021 ◽  
Vol 79 (4) ◽  
pp. 1547-1561
Author(s):  
Rasha H. Mehder ◽  
Brian M. Bennett ◽  
R. David Andrew
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Mouse Model ◽  
Oxidative Damage ◽  
Late Onset ◽  
Dendritic Morphology ◽  
Ca1 Region ◽  
Age Related

Background: Neuronal damage resulting from increased oxidative stress is important in the development of late onset/age-related Alzheimer’s disease (LOAD). We have developed an oxidative stress–related mouse model of LOAD based on gene deletion of aldehyde dehydrogenase 2 (ALDH2), an enzyme important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit AD-like pathologies and a progressive decline in recognition and spatial memory. This progression presumably has a morphological basis induced by oxidative damage. Objective: We performed morphometric analyses in the dorsal hippocampal CA1 region (dCA1) to determine if altered neuronal structure can help account for the progressive cognitive impairment in 3- to 12-month-old KO mice. Methods: Dendritic morphology was quantitatively analyzed by branched structured analysis and Sholl analysis following Golgi-Cox staining in WT mice (148 neurons) versus KO mice (180 neurons). Results: The morphology and complexity of dCA1 pyramidal neurons were similar at age 3 months in WTs and KOs. However, by 6 months there were significant reductions in apical and basal dendritic length, dendrite complexity, and spine density in KO versus WT mice that were maintained through ages 9 and 12 months. Immunostaining for protein adducts of the lipid peroxidation product 4-hydroxynonenal revealed significant increases in staining in dCA1 (but not ventral CA1) by 3 months, increasing through 12 months. Conclusion: This specific and progressive increase in dCA1 oxidative damage preceded detectable synaptic trimming in KO mice, in keeping with studies showing that lesions to dorsal hippocampus primarily impair cognitive memory.

scholarly journals Characterization of monomeric and soluble aggregated Aβ in Down’s syndrome and Alzheimer’s disease brains

2021 ◽  
Vol 754 ◽  
pp. 135894
Author(s):  
Eleni Gkanatsiou ◽  
Charlotte Sahlin ◽  
Erik Portelius ◽  
Malin Johannesson ◽  
Linda Söderberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down's Syndrome ◽  
Down’S Syndrome

scholarly journals Characterization of monomeric and soluble aggregated Aβ in Down’s syndrome and Alzheimer’s disease brains

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Eleni Gkanatsiou ◽  
Charlotte Sahlin ◽  
Erik Portelius ◽  
Malin Johannesson ◽  
Linda Söderberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down's Syndrome ◽  
Down’S Syndrome

Intracellular calcium response is reduced in CD4+ lymphocytes in Alzheimer's disease and in older persons with down's syndrome

1993 ◽  
Vol 14 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Angelika Grossmann ◽  
Walter A. Kukull ◽  
John C. Jinneman ◽  
Thomas D. Bird ◽  
Enrique C. Villacres ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intracellular Calcium ◽  
Older Persons ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Calcium Response ◽  
Cd4 Lymphocytes
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