scholarly journals The Viral Hypothesis in Alzheimer’s Disease: Novel Insights and Pathogen-Based Biomarkers

2020 ◽  
Vol 10 (3) ◽  
pp. 74 ◽  
Author(s):  
Sean X Naughton ◽  
Urdhva Raval ◽  
Giulio M. Pasinetti
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune System ◽  
Antimicrobial Properties ◽  
Significant Risk ◽  
Amyloid Β ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Viral Hypothesis

Early diagnosis of Alzheimer’s disease (AD) and the identification of significant risk factors are necessary to better understand disease progression, and to develop intervention-based therapies prior to significant neurodegeneration. There is thus a critical need to establish biomarkers which can predict the risk of developing AD before the onset of cognitive decline. A number of studies have indicated that exposure to various microbial pathogens can accelerate AD pathology. Additionally, several studies have indicated that amyloid-β possess antimicrobial properties and may act in response to infection as a part of the innate immune system. These findings have led some to speculate that certain types of infections may play a significant role in AD pathogenesis. In this review, we will provide an overview of studies which suggest pathogen involvement in AD. Additionally, we will discuss a number of pathogen-associated biomarkers which may be effective in establishing AD risk. Infections that increase the risk of AD represent a modifiable risk factor which can be treated with therapeutic intervention. Pathogen-based biomarkers may thus be a valuable tool for evaluating and decreasing AD risk across the population.

scholarly journals The Innate Immune System in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Allal Boutajangout ◽  
Thomas Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Late Onset ◽  
Innate Immune ◽  
Amyloid Angiopathy ◽  
Functional Variant ◽  
The Central Nervous System ◽  
Congophilic Amyloid Angiopathy

Alzheimer’s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloidβ(Aβ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

scholarly journals Link between Diabetes and Alzheimer’s Disease Due to the Shared Amyloid Aggregation and Deposition Involving Both Neurodegenerative Changes and Neurovascular Damages

2020 ◽  
Vol 9 (6) ◽  
pp. 1713 ◽  
Author(s):  
Gabriela Dumitrita Stanciu ◽  
Veronica Bild ◽  
Daniela Carmen Ababei ◽  
Razvan Nicolae Rusu ◽  
Alina Cobzaru ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Impact ◽  
Significant Risk ◽  
Amyloid Β ◽  
Detailed Knowledge ◽  
Amyloid Aggregation ◽  
Islet Amyloid ◽  
Type 3 ◽  
Insight Into

Diabetes and Alzheimer’s disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms “diabetes type 3” or “brain diabetes” have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer’s disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

Physical activity in Alzheimer's disease: research in its infancy or why we need more randomized controlled trials

2013 ◽  
Vol 26 (1) ◽  
pp. 7-7 ◽  
Author(s):  
Nicola T. Lautenschlager
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Randomized Controlled Trials ◽  
Physical Inactivity ◽  
Significant Risk ◽  
Controlled Trials ◽  
Randomized Controlled

With the global aging of our societies and predicted increase of cognitive impairment and dementia, it is no surprise that there is an increasing interest in the research community, but also among clinicians and the general population to learn more about how to focus on modifiable protective factors and how to avoid modifiable risk factors. A recent review of systematic reviews and meta-analyses on significant risk factors for Alzheimer's disease (AD) highlighted the importance of diabetes, hypertension, obesity, smoking, depression, cognitive inactivity, and physical inactivity (Barnes and Yaffe, 2011). For physical inactivity, for example, the authors reported that up to one million cases of AD could be prevented globally if a physical inactivity could be reduced by 25%. However, we should not forget about the various stages of prevention, and especially in the field of psychogeriatrics should also ask what preventative measures might be effective for older adults who have already experienced cognitive impairment. So we could focus on a secondary prevention approach for individuals with mild cognitive impairment (MCI) or on a tertiary preventative approach for patients with dementia. The number of randomized controlled trials (RCT) investigating the effectiveness of physical activity on cognition is limited for healthy participants and those with MCI, but is even more sparse for those with dementia. Even with the limited number of studies it often is difficult to compare RCTs due to the huge variation in inclusion and exclusion criteria, methodology, instruments used and outcomes, intervention and duration of interventions, and observations.

Perturbation of the transcriptome: implications of the innate immune system in Alzheimer's disease

2016 ◽  
Vol 26 ◽  
pp. 47-53 ◽  
Author(s):  
Fuhai Song ◽  
Ying Qian ◽  
Xing Peng ◽  
Guangchun Han ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune

Role of the peripheral innate immune system in the development of Alzheimer's disease

2018 ◽  
Vol 107 ◽  
pp. 59-66 ◽  
Author(s):  
Aurélie Le Page ◽  
Gilles Dupuis ◽  
Eric H. Frost ◽  
Anis Larbi ◽  
Graham Pawelec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune

Comorbidity of Cerebrovascular and Alzheimer’s Disease in Aging

2020 ◽  
Vol 78 (1) ◽  
pp. 321-334
Author(s):  
Ying Xia ◽  
Nawaf Yassi ◽  
Parnesh Raniga ◽  
Pierrick Bourgeat ◽  
Patricia Desmond ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrovascular Disease ◽  
Amyloid Β ◽  
Later Life ◽  
Imaging Biomarkers ◽  
Comorbid Condition ◽  
Cross Sectional ◽  
Positron Emission

Background: Cerebrovascular disease often coexists with Alzheimer’s disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. Objective: We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. Methods: A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ–V–, Aβ–V+, Aβ+V–, or Aβ+V+. Results: Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. Conclusion: Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

scholarly journals Cognitive Dispersion Is Not Associated with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Results from the European Prevention of Alzheimer’s Dementia (EPAD) v500.0 Cohort

2020 ◽  
Vol 78 (1) ◽  
pp. 185-194
Author(s):  
Tam Watermeyer ◽  
Alejandra Marroig ◽  
Craig W. Ritchie ◽  
Karen Ritchie ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Aging ◽  
Amyloid Β ◽  
Cost Effective ◽  
Csf Levels ◽  
T Tau

Background: Cognitive dispersion, variation in performance across cognitive domains, is posited as a non-invasive and cost-effective marker of early neurodegeneration. Little work has explored associations between cognitive dispersion and Alzheimer’s disease (AD) biomarkers in healthy older adults. Even less is known about the influence or interaction of biomarkers reflecting brain pathophysiology or other risk factors on cognitive dispersion scores. Objective: The main aim of this study was to examine whether higher cognitive dispersion was associated with cerebrospinal fluid (CSF) levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), and amyloid positivity in a cohort of older adults at various severities of AD. A secondary aim was to explore which AD risk factors were associated with cognitive dispersion scores. Methods: Linear and logistic regression analyses explored the associations between dispersion and CSF levels of Aβ42, t-tau, and p-tau and amyloid positivity (Aβ42 < 1000 pg/ml). Relationships between sociodemographics, APOE ɛ4 status, family history of dementia, and levels of depression and dispersion were also assessed. Results: Dispersion did not emerge as associated with any of the analytes nor amyloid positivity. Older (β= –0.007, SE = 0.002, p = 0.001) and less educated (β= –0.009, SE = 0.003, p = 0.009) individuals showed greater dispersion. Conclusion: Dispersion was not associated with AD pathology, but was associated with age and years of education, highlighting individual differences in cognitive aging. The use of this metric as a screening tool for existing AD pathology is not supported by our analyses. Follow-up work will determine if dispersion scores can predict changes in biomarker levels and/or positivity status longitudinally.

scholarly journals Alzheimer’s Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor α

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1215 ◽  
Author(s):  
Francisco Sáez-Orellana ◽  
Jean-Noël Octave ◽  
Nathalie Pierrot
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Metabolism ◽  
Amyloid Β ◽  
The Elderly ◽  
Special Focus ◽  
Peroxisome Proliferator ◽  
Amyloid Β Peptide ◽  
Peroxisome Proliferator Activated Receptor

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Mutations in genes encoding proteins involved in amyloid-β peptide (Aβ) production are responsible for inherited AD cases. The amyloid cascade hypothesis was proposed to explain the pathogeny. Despite the fact that Aβ is considered as the main culprit of the pathology, most clinical trials focusing on Aβ failed and suggested that earlier interventions are needed to influence the course of AD. Therefore, identifying risk factors that predispose to AD is crucial. Among them, the epsilon 4 allele of the apolipoprotein E gene that encodes the major brain lipid carrier and metabolic disorders such as obesity and type 2 diabetes were identified as AD risk factors, suggesting that abnormal lipid metabolism could influence the progression of the disease. Among lipids, fatty acids (FAs) play a fundamental role in proper brain function, including memory. Peroxisome proliferator-activated receptor α (PPARα) is a master metabolic regulator that regulates the catabolism of FA. Several studies report an essential role of PPARα in neuronal function governing synaptic plasticity and cognition. In this review, we explore the implication of lipid metabolism in AD, with a special focus on PPARα and its potential role in AD therapy.

scholarly journals Innate Immune System and Inflammation in Alzheimer's Disease: From Pathogenesis to Treatment

2014 ◽  
Vol 21 (2-3) ◽  
pp. 79-87 ◽  
Author(s):  
Maria Serpente ◽  
Rossana Bonsi ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune
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