scholarly journals Unmasking selective path integration deficits in Alzheimer’s disease risk carriers

2020 ◽  
Vol 6 (35) ◽  
pp. eaba1394 ◽  
Author(s):  
Anne Bierbrauer ◽  
Lukas Kunz ◽  
Carlos A. Gomes ◽  
Maike Luhmann ◽  
Lorena Deuker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Path Integration ◽  
Disease Risk ◽  
Disease Onset ◽  
Memory Loss ◽  
Grid Cell ◽  
Retrosplenial Cortex ◽  
Spatial Cues ◽  
Spatial Disorientation

Alzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations when no compensatory strategies were available, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, posterior cingulate/retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.

scholarly journals Unmasking selective path integration deficits in Alzheimer’s disease risk carriers

2019 ◽  
Author(s):  
Anne Bierbrauer ◽  
Lukas Kunz ◽  
Carlos A. Gomes ◽  
Maike Luhmann ◽  
Lorena Deuker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Path Integration ◽  
Disease Risk ◽  
Disease Onset ◽  
Memory Loss ◽  
Grid Cell ◽  
Retrosplenial Cortex ◽  
Spatial Cues ◽  
Spatial Disorientation

SummaryAlzheimer’s disease (AD) manifests with progressive memory loss and spatial disorientation. Neuropathological studies suggest early AD pathology in the entorhinal cortex (EC) of young adults at genetic risk for AD (APOE ε4-carriers). Because the EC harbors grid cells, a likely neural substrate of path integration (PI), we examined PI performance in APOE ε4-carriers during a virtual navigation task. We report a selective impairment in APOE ε4-carriers specifically when recruitment of compensatory navigational strategies via supportive spatial cues was disabled. A separate fMRI study revealed that PI performance was associated with the strength of entorhinal grid-like representations, suggesting grid cell dysfunction as a mechanistic explanation for PI deficits in APOE ε4-carriers. Furthermore, retrosplenial cortex was involved in the recruitment of compensatory navigational strategies via supportive spatial cues. Our results provide evidence for selective PI deficits in AD risk carriers, decades before potential disease onset.

scholarly journals Spiritual Fitness: A New Dimension in Alzheimer’s Disease Prevention

2021 ◽  
Vol 80 (2) ◽  
pp. 505-519
Author(s):  
Dharma Singh Khalsa ◽  
Andrew B. Newberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Prevention ◽  
Chronic Stress ◽  
Disease Risk ◽  
Memory Loss ◽  
Well Being ◽  
Cognitive Disability ◽  
Spiritual Wellbeing ◽  
Spiritual Fitness

Background: Religious and spiritual interventions may have an effect on Alzheimer’s disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of chronic stress on cognition, reverse memory loss, and create psychological and spiritual wellbeing, which may reduce multiple drivers of Alzheimer’s disease risk. Objective: To detail a new concept in medicine called Spiritual Fitness, a merging of stress reduction, basic wellbeing, and psycho/spiritual wellbeing to prevent Alzheimer’s disease. Methods: The literature on the topics mentioned above is described, including an in-depth discussion on why and how each are critical to advancing the future of Alzheimer’s disease prevention. The many negative effects of chronic stress, and the benefits of Kirtan Kriya, are reviewed. The four pillars of basic wellbeing, six practical aspects of psychological wellbeing, and the four new non-sectarian features of spiritual fitness are then disclosed. Moreover, instructions on practicing Kirtan Kriya are offered in the Supplementary Material. Conclusion: Religious and spiritual practices, including Kirtan Kriya, are crucial components in the development of enhanced cognition and well-being, which may help prevent and, in some cases, reverse cognitive decline. The key point of this review is that making a commitment to live a brain longevity lifestyle including spiritual fitness is a critically important way for aging Alzheimer’s disease free. We hope that this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability.

scholarly journals Effect of Polygenic Score on Alzheimer’s Disease Risk Depends on Age and APOE Status

2020 ◽  
Author(s):  
Brian Fulton-Howard ◽  
Alison M. Goate ◽  
Robert P. Adelson ◽  
Jeremy Koppel ◽  
Marc L. Gordon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Disease Risk ◽  
Age Of Onset ◽  
Low Cost ◽  
Screening Method ◽  
Disease Onset ◽  
Risk Scores ◽  
Cross Sectional

AbstractPolygenic risk scores (PRS) have the potential to serve as a low-cost, non-invasive screening method for Alzheimer’s disease (AD). However, to what extent age and the Apolipoprotein E-ε4 (APOE4) risk allele influence the effect of PRS is underexplored. In a cohort of 346 superager controls (age ≥ 90 years), 2,930 controls (age 60-89) and 1,760 AD cases, we computed APOE-independent PRS for AD. When using superager controls, subjects with PRS in the top decile had nearly five times greater odds of having AD than subjects in the lowest decile (OR=4.91, P=2.24×10−6). In our cross-sectional cohort, PRS modifies the age of onset for AD among APOE4 carriers, but not among non-carriers. Among APOE4 carriers, PRS in the top decile was associated with a five years earlier AD onset than the lowest decile (70.0 vs 75.0 years; t-test P=2.4×10−5). These findings suggest that APOE-independent genetic risk disproportionally affects younger APOE4 carriers, leading to earlier disease onset, while older controls carry less genetic risk.

scholarly journals A Novel Study and Meta-Analysis of the Genetic Variation of the Serotonin Transporter Promoter in the Italian Population Do Not Support a Large Effect on Alzheimer's Disease Risk

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Letizia Polito ◽  
Francesca Prato ◽  
Serena Rodilossi ◽  
Eleonora Ateri ◽  
Daniela Galimberti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Odds Ratio ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
Meta Analysis ◽  
Memory Loss ◽  
Genetic Effect ◽  
Italian Population ◽  
S Allele

Alzheimer’s disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped theSLC6A4promoter functional variantrs25531(A→G). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between5-HTTLPRand AD (odds ratio for the L-allele versus the S-allele: 0.74, associatedPvalue = .03), while no difference was found for thers25531. A meta-analysis of studies in Italy assessing5-HTTLPRand AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associatedPvalue = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk.

scholarly journals A New Presenilin 1 (Psen1) Mutation (p.Cys263Trp) as a Cause of Both Early and Late-Onset Alzheimer’s Disease in a Large Italian Family

2021 ◽  
Vol 22 (12) ◽  
pp. 6215
Author(s):  
Rosanna Tortelli ◽  
Davide Seripa ◽  
Chiara Zecca ◽  
Maria Teresa Dell’Abate ◽  
Paola Bisceglia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Psychiatric Symptoms ◽  
Late Onset ◽  
Memory Loss ◽  
Lewy Body Dementia ◽  
The Other ◽  
Spatial Disorientation ◽  
Phenotype Variability ◽  
Psen1 Gene

Mutations in the PSEN1 gene are the most common cause of autosomal dominant Alzheimer’s disease, and are characterized by a high phenotype variability. This study describes a five-generation family, with a prevalent late-onset of the disease and a high frequency of depression, in which a new missense mutation (c.789T > G, p.Cys263Trp) in exon 8 of the PSEN1 gene was found. Only the proband presented an early onset at the age of 45 with attention deficit, followed by spatial disorientation, psychiatric symptoms and parkinsonian signs. The other two cases had a late onset of the disease and a typical presentation with memory loss. Both were characterized by a high level of anxiety and depression. The disease course was different with signs of Lewy body dementia for the proband’s mother, and pyramidal involvement and a shorter disease duration for the proband’s maternal aunt. The other eight cases with late-onset dementia and three cases with a long history of depression have been reported in the family pedigree, underlying the high phenotype variability of PSEN1 mutations.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

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