Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Xia, Xian; Jiang, Quanlong; McDermott, Joseph; Han, Jing‐Dong J.

doi:10.1111/acel.12802

Cited by 235 publications

(163 citation statements)

References 182 publications

(197 reference statements)

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“…Although age is the most important risk factor, genetic risk factors have also been described . Single genes commonly associated with Alzheimer's disease and believed to be causative (early onset) include chromosome 21 APP, chromosome 14 PSEN1, and chromosome 1 PSEN2 .…”

Section: Alzheimer's Disease Overviewmentioning

confidence: 99%

Oral health care for patients with Alzheimer's disease: An update

Marchini

Ettinger

Caprio

et al. 2019

Special Care in Dentistry

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Alzheimer's disease and related disorders (ADRD) are among the age‐associated chronic conditions that are most challenging to health care systems around the globe, as patients with dementia require full‐time, intensive care for multiple years. Oral health care is negatively impacted by cognitive decline, and consequently poor oral health is common among people with ADRD. Poor oral health status is linked with many undesirable consequences for the well‐being of people with ADRD, from excruciating local pain to life‐threatening conditions, as aspiration pneumonia. In this paper, the authors provide an update on the most current concepts about Alzheimer's disease epidemiology, etiology, and management, current oral health care for patients with Alzheimer's disease, oral health promotion strategies for this population, as well as current research and future direction for improving oral health care for patients with Alzheimer's disease. It concludes that oral health care should be included in the patient's routine health care as early as possible in the progression of Alzheimer's disease for preventing rapid oral health deterioration. Establishing oral hygiene routines and providing dental treatment that is customized to the patients’ individual needs and disease stage are important to achieve good oral health outcomes and prevent quality of life decline.

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Section: Alzheimer's Disease Overviewmentioning

confidence: 99%

Oral health care for patients with Alzheimer's disease: An update

Marchini

Ettinger

Caprio

et al. 2019

Special Care in Dentistry

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“…The prevalence of late‐onset Alzheimer's disease (LOAD), dementia, and cognitive impairment is growing with the aging population, and reliable plasma/serum biomarkers that can be used for pre‐clinical diagnosis, monitoring and prediction of cognitive decline, onset of cognitive impairment, and for suggesting therapeutic targets are lacking (Cheng et al, ; Xia, Jiang, McDermott, & Han, ). Recent studies have shown that the development of drugs related to genetic findings is more likely to be successful than average (Nelson et al, ), and since the gene APOE is the most robust genetic variant associated with cognitive change and LOAD, it is an obvious target.…”

Section: Introductionmentioning

confidence: 99%

A serum protein signature of APOE genotypes in centenarians

et al. 2019

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The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late‐onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e 2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e 2, with aptamer‐based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late‐onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e 2 molecularly may preserve cognitive function.

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“…It is of note that decline in RAR expression and RA signaling is also evident in the aging mouse and that this is reversible by RA treatment [66]. Although the cognitive decline in AD and normal aging each has its distinguishable features, there is also significant overlap between the two in genetic susceptibility and epigenetic input [67,68]. Epigenetic modification has been proposed in the treatment of both AD [69] and aging [70].…”

Section: Discussionmentioning

confidence: 99%

Decay in Retinoic Acid Signaling in Varied Models of Alzheimer’s Disease and In-Vitro Test of Novel Retinoic Acid Receptor Ligands (RAR-Ms) to Regulate Protective Genes

Khatib

Chisholm

Whiting

et al. 2020

JAD

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Retinoic acid has been previously proposed in the treatment of Alzheimer's disease (AD). Here, five transgenic mouse models expressing AD and frontotemporal dementia risk genes (i.e., PLB2 APP , PLB2 TAU , PLB1 Double , PLB1 Triple , and PLB4) were used to investigate if consistent alterations exist in multiple elements of the retinoic acid signaling pathway in these models. Many steps of the retinoic acid signaling pathway including binding proteins and metabolic enzymes decline, while the previously reported increase in RBP4 was only consistent at late (6 months) but not early (3 month) ages. The retinoic acid receptors were exceptional in their consistent decline in mRNA and protein with transcript decline of retinoic acid receptors ␤ and ␥ by 3 months, before significant pathology, suggesting involvement in early stages of disease. Decline in RBP1 transcript may also be an early but not late marker of disease. The decline in the retinoic acid signaling system may therefore be a therapeutic target for AD and frontotemporal dementia. Thus, novel stable retinoic acid receptor modulators (RAR-Ms) activating multiple genomic and non-genomic pathways were probed for therapeutic control of gene expression in rat primary hippocampal and cortical cultures. RAR-Ms promoted the non-amyloidogenic pathway, repressed lipopolysaccharide induced inflammatory genes and induced genes with neurotrophic action. RAR-Ms had diverse effects on gene expression allowing particular RAR-Ms to be selected for maximal therapeutic effect. Overall the results demonstrated the early decline of retinoic acid signaling in AD and frontotemporal dementia models and the activity of stable and potent alternatives to retinoic acid as potential therapeutics.

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Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Cited by 235 publications

References 182 publications

Oral health care for patients with Alzheimer's disease: An update

Oral health care for patients with Alzheimer's disease: An update

A serum protein signature of APOE genotypes in centenarians

Decay in Retinoic Acid Signaling in Varied Models of Alzheimer’s Disease and In-Vitro Test of Novel Retinoic Acid Receptor Ligands (RAR-Ms) to Regulate Protective Genes

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