scholarly journals Response: Commentary: Age-related neurodegenerative disease research needs aging models

Author(s):  
Ian P. Johnson
Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2383
Author(s):  
Suet Theng Beh ◽  
Carlye Frisch ◽  
David A. Brafman ◽  
Jared Churko ◽  
Jessica E. Walker ◽  
...  

The Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program at Banner Sun Health Research Institute (BSHRI) is a longitudinal clinicopathological study with a current enrollment of more than 900 living subjects for aging and neurodegenerative disease research. Annual clinical assessments are done by cognitive and movement neurologists and neuropsychologists. Brain and body tissues are collected at a median postmortem interval of 3.0 h for neuropathological diagnosis and banking. Since 2018, the program has undertaken banking of scalp fibroblasts derived from neuropathologically characterized donors with Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases. Here, we describe the procedure development and cell characteristics from 14 male and 15 female donors (mean ± SD of age: 83.6 ± 12.2). Fibroblasts from explant cultures were banked at passage 3. The results of mRNA analysis showed positive expression of fibroblast activation protein, vimentin, fibronectin, and THY1 cell surface antigen. We also demonstrated that the banked fibroblasts from a postmortem elderly donor were successfully reprogramed to human-induced pluripotent stem cells (hiPSCs). Taken together, we have demonstrated the successful establishment of a human autopsy-derived fibroblast banking program. The cryogenically preserved cells are available for request at the program website of the BSHRI.


Science ◽  
2015 ◽  
Vol 349 (6252) ◽  
pp. 1259504-1259504 ◽  
Author(s):  
P. T. J. Johnson ◽  
J. C. de Roode ◽  
A. Fenton

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110443
Author(s):  
Paul A. Oakley

A subset of victims who experience concussion suffer from persistent symptoms spanning months to years post-injury, termed post-concussion syndrome (PCS). Problematically, there is lack of consensus for the treatment of PCS. Concussion injury involves a neurometabolic cascade leading to oxidative stress and neuroinflammation which parallels the oxidative stress loading occuring from age-related neurodegenerative conditions. Historical and recent evidence has emerged showing the efficacy of low-dose radiation therapy for many human diseases including neurodegenerative diseases such as Alzhiemer’s disease (AD). Due to the pathognomonic similarities of oxidative stress and neuroinflammation involved in PCS and neurodegenerative disease, treatments that prove successful for neurodegenerative disease may prove successful for PCS. Recently, low-dose ionizing radiation therapy (LDIR) has been documented to show a reversal of many symptoms in AD, including improved cognition. LDIR is thought to induce a switching from proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype. In other words, a continual upregulation of the adaptive protection systems via LDIR induces health enhancement. It is hypothesized LDIR treatment for PCS would mimic that seen from early evidence of LDIR treatment of AD patients who suffer from similar oxidative stress loading. We propose the application of LDIR is a promising, untapped treatment for PCS.


2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Jessica Klusek ◽  
Amanda Fairchild ◽  
Carly Moser ◽  
Marsha R. Mailick ◽  
Angela John Thurman ◽  
...  

Abstract Background Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. Methods Forty-five women with the FMR1 premutation aged 35–64 years at study entry participated in 1–5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. Results Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. Conclusions Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation.


Author(s):  
Nathan F. Clement ◽  
John C. DeWitt ◽  
Matthew P. Frosch ◽  
Maria Martinez-Lage ◽  
Wesley R. Samore ◽  
...  

Context.— Postmortem evaluation for neurodegenerative disease is expensive in time and materials. These challenges can be met by implementing simpler sampling protocols while preserving anatomic relations. Objective.— To determine the diagnostic effectiveness and cost-effectiveness of a simplified brain blocking protocol compared with the standard blocking protocol used in our Alzheimer disease research center (ADRC). Design.— We prospectively compared the neuropathologic diagnoses established from our standard 19-cassette/19 brain sites ADRC protocol to a simplified 6-cassette/12 brain sites protocol in 52 consecutive cases. The simplified protocol generated 14 slides for comparison to 52 slides from our standard protocol. Results.— Compared with the ADRC protocol the simplified protocol produced Alzheimer Disease Neuropathologic Changes probability scores that were the same in 50 of 52 cases (r = 0.99). Staging for Lewy pathology was equivalent in 45 of 52 (r = 0.98), scoring for cerebral amyloid angiopathy was equivalent in 48 of 52 (r = 0.97), and grading for arteriolosclerosis was the same in 45 of 52 cases (r = 0.92). Progressive supranuclear palsy (n = 4), multiple system atrophy (n = 2), and corticobasal degeneration (n = 1) could be diagnosed by either protocol independently. The estimated savings per case was 72% or $1744.89 ($2436.37 [ADRC] versus $691.48 [simplified]). Conclusions.— The diagnosis of neurodegenerative disease at autopsy can be done accurately with a less expensive, simplified protocol. Our protocol is similar to those of previously published approaches, but it has a simpler organization scheme. This method should be valuable to institutions where autopsy cost considerations may be important.


2018 ◽  
Vol 55 ◽  
pp. 128-133 ◽  
Author(s):  
Angus D. Macleod ◽  
Rachel Henery ◽  
Paul C. Nwajiugo ◽  
Nicholas W. Scott ◽  
Robert Caslake ◽  
...  

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