The bivariate distribution of amyloid- β and tau: relationship with established neurocognitive clinical syndromes

We examined these clinical groups in relation to the bivariate distribution of amyloid and tau PET values. Individuals were grouped into amyloid (A)/tau (T) quadrants based on previously established abnormality cut points of s tandardized uptake value ratio 1.48 (A) and 1.33 (T). Individual participants largely fell into one of three amyloid/tau quadrants: low amyloid and low tau (A−T−), high amyloid and low tau (A+T−), or high amyloid and high tau (A+T+). Seventy per cent of cognitively unimpaired and 74% of FTD pa rticipants fell into the A−T− quadrant. Participants with mild cognitive impairment spanned the A−T− (42%), A+T− (28%), and A+T+ (27%) quadrants. Probable dementia with Lewy body participants spanned the A−T− (38%) and A+T− (44%) quadrants. Most (89%) participants with Alzheimer clin ical syndrome fell into the A+T+ quadrant. These data support several conclusions. First, among 1343 participants, abnormal tau PET rarely occurred in the absence of abnormal amyloid PET, but the reverse was common. Thus, with rare exceptions, amyloidosis appears to be required for high levels of 3R /4R tau deposition. Second, abnormal amyloid PET is compatible with normal cognition but highly abnormal tau PET is not. These two conclusions support a dynamic biomarker model in which Alzheimer’s disease is characterized first by the appearance of amyloidosis and later by tauopathy, with tauopat hy being the proteino...
Source: Brain - Category: Neurology Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We examined, in a community-based population (N = 777, aged 50–95) (1) what variables were associated with each of the CSF (N) markers, and (2) whether the variables associated with each marker differed by increased brain amyloid. CSF T-tau was measured with an automated electrochemiluminescence Elecsys immunoassay; NfL and Ng were measured with in-house enzyme-linked immunosorbent assays.ResultsMultiple variables were differentially associated with CSF NfL and T-tau levels, but not Ng. Most associations were attenuated after adjustment for age and sex. T-tau had the strongest association with cognition in ...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - Category: Geriatrics Source Type: research
In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise. Methods of Inducing Cellular Damage are Rarely Relevant to Aging, and the Details Matter https://www.fightaging.org/archives/2019/08/methods-of-inducing-cellular-damage-are-rarely-relevant-to-aging-and-the-details-matter/ One of the major challenges in aging research is determining whether or not models of cellular or organismal damage and its consequences are in any way relevant to the natural processes of aging. One can hit a brick with...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSIONS: We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia. PMID: 31309997 [PubMed - in process]
Source: Revista de Neurologia - Category: Neurology Authors: Tags: Rev Neurol Source Type: research
Abstract Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms such as activity and sleep disturbances. AD patients typically experience increased sleep fragmentation, excessive daytime sleepiness and night-time insomnia. Here, we sought to investigate the link between sleep architecture, cognition and amyloid pathology in the APP23 amyloidosis mouse model for AD. By means of polysomnographic recordings the sleep-wake cycle of freely-moving APP23 and wild-type (WT) littermates of 3, 6 and 12 mon...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research
Alzheimer’s disease (AD) is the most widespread form of dementia, affecting about 45 million people worldwide. Although the β-amyloid peptide (Aβ) remains the most acknowledged culprit of AD, the multiple failures of Aβ-centric therapies call for alternative therapeutic approaches. Conceivably, the complexity of the AD neuropathological scenario cannot be solved with single-target therapies, so multiple-target approaches are needed. Core targets of AD to date are soluble oligomeric Aβ species and neuroinflammation, in an intimate detrimental dialogue. Aβ oligomers, the most neurotoxic species...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we evaluated the effect of chronic oral quercetin administration (100 mg/kg) on neurodegeneration markers and cognitive and emotional deficits in a triple transgenic Alzheimer’s disease (3xTg-AD) mouse model using histological and behavioral analyses. Our results suggest that long-term (12 months) oral preventive treatment with quercetin has significant effects on β-amyloidosis reduction and tends to decrease tauopathy in the hippocampus and amygdala. These decreases positively affected the cognitive functional recovery (without modifying the emotional skills) of 3xTg-AD mice. These findin...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In conclusion, there is solid evidence that obesity deregulates cellular mechanisms related to nutrient sensing. Altered Intercellular Communication It is accepted that aging impacts the organism at the cellular level, but also decreases the capacity of cells of an organism to interact. During aging, there is a decreased communication at the neuronal, neuroendocrine, and endocrine levels. Two of the most compelling examples of impaired communication are inflammaging and immunosenescence. The inflammaging phenotype results in elevated cytokines. These cytokines can accelerate and propagate the aging process. T...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Altoida is combining artificial intelligence, machine learning, and augmented reality to help detect Alzheimer’s disease. The Houston, TX-based company has struck a chord with venture capitalists, raising $6.3 million in a series A round. The financing was led by M Ventures, the corporate venture capital arm of the science and technology company Merck KGaA, Darmstadt, Germany, with participation from Grey Sky Venture Partners, VI Partners AG, Alpana Ventures, and FYRFLY Venture Partners. The new capital will be used to further expand Altoida's presence worldwide with an immediate focus on commercializati...
Source: MDDI - Category: Medical Devices Authors: Tags: Assembly and Automation Source Type: news
Many neurodegenerative conditions are associated with the accumulation of forms of metabolic waste in the central nervous system, protein aggregates that form solid deposits between or within cells. Tauopathies such as frontotemporal dementia are associated with tau aggregates, synucleinopathies such as Parkinson's disease with α-synuclein, and amyloidoses with varying forms of amyloid, such as the amyloid-β found in elevated amounts in Alzheimer's disease patients. Alzheimer's itself is an amyloidosis that also becomes a tauopathy in its later stages. These protein aggregates and their surrounding halos of harm...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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