Commentary on “Lowering the risk of Alzheimer's disease: Evidence-based practices emerge from new research.” Prevention of Alzheimer disease

Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease–related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease–Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

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A STUDY OF EVIDENCE-BASED COGNITIVE REHABILITATION PROGRAMS FOR ALZHEIMER’S DISEASE AND DEMENTIA

Innovation in Aging ◽

10.1093/geroni/igy023.000 ◽

2018 ◽

Vol 2 (suppl_1) ◽

pp. 1-1

Author(s):

M E Felver ◽

S L Sereda

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Rehabilitation ◽

Evidence Based ◽

Rehabilitation Programs

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Attention and inhibition in Mild Cognitive Impairment and Alzheimer's Disease

Escritos de Psicología / Psychological Writings ◽

10.24310/espsiescpsi.v6i3.13288 ◽

2013 ◽

Vol 6 (3) ◽

pp. 43-50

Author(s):

Clara Zancada-Menéndez ◽

Patricia Sampedro-Piquero ◽

Azucena Begega ◽

Laudino López ◽

Jorge Luis Arias

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Reaction Time ◽

Alzheimer Disease ◽

Neuropsychological Test ◽

Reaction Times ◽

Stop Signal Task ◽

Healthy Controls

Mild cognitive impairment is understood as a cognitive deficit of insufficient severity to fulfil the criteria for Alzheimer’s disease. Many studies have attempted to identify which cognitive functions are most affected by this type of impairment and which is the most sensitive neuropsychological test for early detection. This study investigated sustained and selective attention, processing speed, and the inhibition process using a sample of people divided into three groups mild cognitive impairment, Alzheimer disease and cognitively healthy controls selected and grouped based on their scores in the Mini Mental State Examination and Cambridge Cognitive Examination-revised. Three tests from the Cambridge Neuropsychological Test Automated Battery (Motor Screening Task, Stop Signal Task and Reaction time) were used as well as the d2 attention test. The results show that that participants with mild cognitive impairment and Alzheimer disease showed lower levels of concentration compared with the cognitively healthy controls group in the d2 test and longer reaction times in the Cambridge Neuropsychological Test Automated Battery, although the differences were not marked in the latter test. The impairments in basic cognitive processes, such as reaction time and sustained attention, indicate the need to take these functions into account in the test protocols when discriminating between normal aging and early and preclinical dementia processes.

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Modeling the β secretase cleavage site and humanizing Amyloid-Beta Precursor Protein in rat and mouse to study Alzheimer Disease.

10.21203/rs.3.rs-32032/v1 ◽

2020 ◽

Author(s):

Lutgarde Serneels ◽

Dries T'Syen ◽

Laura Perez-Benito ◽

Tom Theys ◽

Bart De Strooper

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amino Acid ◽

Alzheimer Disease ◽

Early Onset ◽

Computational Modelling ◽

Original Strain ◽

Rodent Models ◽

App Processing

Abstract Background Three amino acid differences between rodent and human APP affect medically important features including β-secretase cleavage of APP and aggregation of the Aβ peptide(1–3). Most rodent models for Alzheimer’s disease (AD) are therefore based on the human APP sequence expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well biochemical aspects of the disease such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations due to genes affected in or close to the insertion sites of the mini-genes(4,5). Knock-in strategies introducing clinical mutants in a humanized endogenous rodent APP sequence(6) represent useful improvements, but need to be compared with appropriate humanized wild type (WT) mice.Methods Computational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse as well as in the rat by a CRISPR-Cas9 approach. These new models, termed mouse and rat App hu/hu , express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene.Results We show that the three amino acid substitutions in the rodent sequence lower the affinity of APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to their WT rodent original strain. These models represent suitable controls or starting points for studying the effect of transgenes or knock-in mutations on APP processing(6). We introduced the early-onset familial Alzheimer disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene and provide an initial characterization of Aβ processing in this novel rat AD model.Conclusion The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo and allow to implement the use of human Aβ Elisa which is more sensitive than their rodent counterpart. These animals will be made available to the research community.

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The Genetic Research in Alzheimer Disease (GERALD) Initiative Finds rs9320913 as a Neural eQTL of lincRNA AL589740.1

International Journal of Alzheimer s Disease ◽

10.1155/2021/3064224 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Lidia Lopez-Gutierrez ◽

José María García-Alberca ◽

Silvia Mendoza ◽

Esther Gris ◽

María Paz De la Guía ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Alzheimer Disease ◽

Mental State ◽

Fluid Intelligence ◽

Educational Achievement ◽

Disease Risk ◽

Genetic Research ◽

Gene Desert ◽

Factors Affecting

Alzheimer’s disease is the most common cause of dementia worldwide, and longitudinal studies are crucial to find the factors affecting disease development. Here, we describe a novel initiative from southern Spain designed to contribute in the identification of the genetic component of the cognitive decline of Alzheimer’s disease patients. The germline variant rs9320913 is a C>A substitution mapping within a gene desert. Although it has been previously associated to a higher educational achievement and increased fluid intelligence, its role on Alzheimer’s disease risk and progression remains elusive. A total of 407 subjects were included in the study, comprising 153 Alzheimer disease patients and 254 healthy controls. We have explored the rs9320913 contribution to both Alzheimer disease risk and progression according to the Mini-Mental State Exams. We found that rs9320913 maps within a central nervous system lincRNA AL589740.1. eQTL results show that rs9320913 correlated with the brain-frontal cortex ( beta = − 0.15 , p value = 0.057) and brain-spinal cord (beta of -0.23, p value = 0.037). We did not find rs9320913 to be associated to AD risk, although AA patients seemed to exhibit a less pronounced Mini-Mental State Exam score decline.

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P1-371: New research criteria for the diagnosis of Alzheimer's disease applied in a memory clinic population

Alzheimer s & Dementia ◽

10.1016/j.jalz.2008.05.953 ◽

2008 ◽

Vol 4 ◽

pp. T327-T328 ◽

Cited By ~ 1

Author(s):

Femke H. Bouwman ◽

Nicolaas A. Verwey ◽

Martin Klein ◽

Yolande A.L. Pijnenburg ◽

Astrid Kok ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Clinic ◽

New Research ◽

Research Criteria ◽

Clinic Population

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Evidence-Based Practice with Alzheimer’s Disease and Dementia

Evidence-Based Counseling and Psychotherapy for an Aging Population ◽

10.1016/b978-0-12-374937-6.00015-2 ◽

2009 ◽

pp. 321-341

Author(s):

Morley D. Glicken

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Evidence Based Practice ◽

Evidence Based

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Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD spectrum diseases

Brain ◽

10.1093/brain/awaa196 ◽

2020 ◽

Vol 143 (8) ◽

pp. 2398-2405 ◽

Cited By ~ 3

Author(s):

Shinsuke Ishigaki ◽

Yuichi Riku ◽

Yusuke Fujioka ◽

Kuniyuki Endo ◽

Nobuyuki Iwade ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Alzheimer Disease ◽

Progressive Supranuclear Palsy ◽

Corticobasal Degeneration ◽

Pick's Disease ◽

Pick’S Disease ◽

Subsequent Increase ◽

Fused In Sarcoma ◽

Wide Range

Abstract Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS/FTLD (ALS/FTLD-FUS), TDP-43-related ALS/FTLD (ALS/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease, or Pick’s disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS/FTLD-FUS, ALS/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer’s disease or Pick’s disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R/3R-tau was elevated in cases with ALS/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases.

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