The Alzheimer's Solution

1 day ago

#tauprotein #alzheimerstest #biomarkers

Over the last few years, I've posted here on the development of tau and beta-amyloid protein blood-based biomarkers in the assessment for Alzheimer's disease.

For example, in November-2020, I posted here that the much anticipated announcement for the first beta-amyloid blood test (Aβ42/40 ratio) for clinical use was finally here.

Similarly, blood test reports for plasma tau protein (phospho-Tau217) have shown significant promise for adjunctive assessment options to the Aβ42/40 ratio assessment.

Recent studies funded by the National Institute on Aging have shown that the blood samples of phospho-Tau217 (p-tau181) can serve as a viable biomarker for the early detection for early-onset AD many years before the onset of symptoms.

One such study concluded that "Blood measurements of ptau217 were also about 90% accurate at distinguishing people who later developed symptoms of dementia."

Plus, p-tau217 blood levels were deemed to be good as PET imaging and cerebrospinal testing for the specific development of AD.

And in 2023 (9/2023), I reported on the blood test—PrecivityAD2™—that includes a set of significant tau protein blood biomarkers—phosphorylated and nonphosphorylated forms of the p-tau217 and p-tau181 proteins.

Note that PrecivityAD2™is available to physicians from C₂N Diagnostics.

The backstory on the C₂N Diagnostics menu of tests is that the technology that underlies their p-tau217 assessment was developed by researchers at Washington University School of Medicine in St. Louis (WashU).

Now, and their most recent announcement, WashU researchers have developed another tau blood biomarker—MTBR-tau243.

The WashU report linked to here includes their rationale on the importance of another complimentary tau protein aggregate assessment (MTBR-tau243) that provides invaluable insights into the progression of Alzheimer's disease, and also is specific to Alzheimer's dementia.

The MTBR-tau243 evaluation viability was based on data extracted and validated from two cohorts that included individuals in the:

- presymptomatic stage of Alzheimer's disease (no cognitive impairment),

-through early-stage disease with mild cognitive impairments, and

- individuals with late symptomatic disease when patients exhibit full-blown dementia.

"The researchers’ analysis showed that blood MTBR-tau243 levels reflected the amount of tau tangles in the brain with 92% accuracy", and were independent of beta-amyloid aggregates.

Note well well (not included in the report) that neuroimaging tests such as PET, MRI and SPECT are accepted as valuable adjunctive tools for a biomarker guided approach for early diagnosis and treatment.

More importantly, while the tau and beta-amyloid tests are indeed important in the assessment of Alzheimer's disease stages—early to late stage—the most opportune timing in the evaluation of risk for late-onset Alzheimer's disease (LOAD) is midlife or earlier, and before any noticeable cognitive impairment is noticeable.

In combination with genetic profiling, cardiometabolic risk assessments, evaluations for hormone imbalances and deficiencies, and cognitive performance tests and others, such evaluations can also shed light on person's risk and vulnerability for LOAD as they age.

Don't wait to be diagnosed.

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Highly accurate blood test diagnoses Alzheimer’s disease, measures extent of dementia | WashU Medicine

medicine.washu.edu

Could help determine which patients are likely to benefit from new Alzheimer’s drugs

The Alzheimer's Solution

1 month ago

#metabolicsyndrome #type3diabtes #alzheimersrisk

The incidence of age-related diseases such as type 2 diabetes/metabolic syndrome, and heart disease (cardiometabolic disease) and the risk factors associated with them, namely obesity, continues to escalate in a pandemic-like manner around the world.

Indeed, type 2 diabetes/metabolic syndrome, hypertension, obesity and cardiovascular disease (cardiometabolic disease), and the diet and lifestyle factors associated with them, vastly increases the risk for vascular dementia and AD, but they also MODIFIABLE risk factors. (The Diabetic Brain in Alzheimer's Disease).

The report linked to here highlights key genetic, and metabolic risk factor linkages which are strongly linked to the incidence of dementia and late-onset Alzheimer's disease (LOAD) including:

- ApoE4 gene variant

- disrupted fat metabolism (e.g., cholesterol/triglyceride metabolism)

- insulin function (e.g., insulin resistance)

- beta-amyloid aggregations (e.g., plaque)

- neuroinflammation (brain inflammation)

- brain shrinkage (atrophy)

The body and brain metabolic alterations linked to glucose and fat metabolism, insulin function derangements, and the the subsequent pro-inflammatory cascades driven by metabolic disease are again, modifiable risk factors and are reversible.

Dietary intervention therapies including ketogenic and caloric restriction therapies—the latter is not mentioned in the report—have an excellent track record of modifying the disease trajectories associated with metabolic disease and chronic inflammation.

Low-carb mediterranean diets are and excellent dietary management intervention as well.

Note: ketogenic diets are high fat diets.

Caution with the persistent caveat of "high-fat" dangers as it is often misinterpreted. Healthy fats derived from plant foods, and organic meat and dairy fats are a great source of nutrients.

Think ahead and take control of your risk; midlife is a critical juncture in the opportunity to do so.

More than one-third of the world-wide cases associated with the development of vascular dementia, and LOAD are linked to modifiable risk factors.

Seek the support of an experienced guide, and begin the process of understanding your risk for dementia and late-onset Alzheimer's disease through the assessment and evaluation of risk biomarkers, which can also shed invaluable insights for living younger, longer.

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New review sheds light on links between Alzheimer's and metabolic syndrome

www.news-medical.net

Alzheimer's disease (AD), the most common form of dementia, continues to remain one of modern medicine's greatest challenges.

The Alzheimer's Solution

2 months ago

#braindetoxification #autophagy #proteostasis

How do we remove "harmful protein accumulations" from the brain such as beta-amyloid or tau protein aggregates that are neurotoxic and hallmark pathologies associated with the development of Alzheimer's disease?

The same query can be made with the accumulation of alpha-synuclein which is linked to the development of Parkinson's.

The maintenance of protein synthesis, turnover, degradation, and clearance mechanisms are essential components to the loss of protein homeostasis or proteostasis—a hallmark of aging.

I'll briefly describe 3 critical mechanisms in brain proteostasis that are critical features of brain health and the prevention of neurodegenerative disorders such as Parkinson's and Alzheimer's disease.

First, autophagy is often described as a cellular “garbage removal” process that is activated in response to various types of cellular stressors, including nutrient deprivation/ energy deficits, and oxidative stress.

Over the past two decades, the role of autophagy in delaying aging and reversing age-related diseases has yielded a cornucopia of remarkable insights.

The autophagic clearance and recycling of dysfunctional or damaged goods is a normal cellular housekeeping activity and a critical component in body-brain detoxification.

Similarly, the microglia—the brain's immune cells—engulf pathogens (phagocytize), neurotoxic tau and protein protein aggregates, and other brain debris for degradation.

Additionally, the role of the ubiquitin–proteasome system (UPS)—a critical protein degradation, clearance and recycling system that works in concert with autophagy.

The ubiquitin–proteasome system (UPS), is composed of proteasomes—a protein degrading complex, and ubiquitin which is another protein that essentially tags other proteins destined for proteasomal degradation.

The transport of beta-amyloid across the blood brain barrier, and by upregulating autophagy—the intracellular debris and recycling system are also key brain detoxification mechanisms.

The glymph-lymph system of the brain is another vital component to reducing the amyloid and tau protein load in the brain is by removing it through the meningeal lymphatics and the downstream glymphatic network.

As with all body-brain proteins that are derived from DNA transcription and translation dynamics that results in protein synthesis in cellular ribosomes, gene mutations associated with genetic expression pathways changes how the efficiency of such DNA coding and protein synthesis ultimately works in one biological homeostasis mechanism or another.

Sometimes for the better, and sometimes not.

With regard to autophagy and other brain detoxification of damaged and toxic proteins that are degraded and removed from the central nervous system, a host of gene mutations or variants are linked to the impairment of brain detoxification mechanisms.

A few such gene variants are highlighted in the report linked to here, and note the emphasis the late-onset Alzheimer's disease (LOAD) genetic risk factor, ApoE4, which I've reported on here on Facebook numerous times.

I delineate the various pathways linked to an increased risk for LOAD associated with the ApoE4 genetic variant in my book, and I in my podcast series on brain detoxification I describe how important autophagy and other protein degradation and clearance pathways are in maintaining brain health and reducing your risk for dementia as you age.

Here is the link to part 3 brain detoxification podcast series on "Autophagy and the Synergistic Proteasomal Degradation System in Brain Detoxification"

podcasts.apple.com/us/podcast/brain-detoxification-part-3-autophagy-and-the/id1614865183?i=100058...

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Alzheimer’s and Parkinson’s linked to aging brain’s failing waste disposal

www.news-medical.net

New research uncovers how declining protein clearance mechanisms with age lead to Alzheimer’s, Parkinson’s, and other neurodegenerative diseases—offering hope for targeted therapies to slow or p...

The Alzheimer's Solution

3 months ago

#braintraining #neuroplasticity #dementiaprevention

Brain Training in the improvement of cognitive function and modifying the cognitive decline associated with dementia has been the subject of several studies with mixed outcomes.

In a report linked to here, the case is made for what constitutes a "brain training" intervention (BrainHQ) that is based on sound and proven model that delivers on significant improvements in cognitive performance.

For example, "the IMPACT study" published in 2009, utilized a "Cognitive Training Program"—BrainHQ— in 487 adults aged 65 and older individuals that included a control group that did not receive any specialized brain training intervention.

The group that underwent an 8 week computerized cognitive training program "showed significant improvements on multiple secondary measures of attention and memory."

Prior to the IMPACT study , the ACTIVE study (2002) which recruited 2832 older individuals, aged 65 to 94 years, analyzed the effects of 3 "different cognitive training programs on cognitive function and time to dementia."

1. In-person training on verbal memory skills
2. In-person training on reasoning and problem-solving*
3. Computer-based speed-of-processing training on visual attention

A 10 session training intervention and each session was conducted over a 5- to 6-week period with booster trainings at 11 and 35 months.

Follow-up cognitive evaluations were at 1, 2, 3, 5, and 10 years.

Overall, the study "demonstrated that cognitive interventions helped normal elderly individuals to perform better on multiple measures of the specific cognitive ability for which they were trained".

Plus, the "speed-of-processing training"* (now part of BrainHQ) showed a 29% lower risk for dementia over the individuals that did not receive the training, and the training was superior to the other two training programs which showed "no net effect" gains in measures of cognitive ability.

More recently, the SYNERGIC study (2023), which included vitamin D and exercise (aerobic-resistance ) along with cognitive training program (Neuropeak), showed that "older adults with mild cognitive impairment receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent."

Vitamin D supplementation had no effect.

The article review linked to here also included commentary from a host of experienced professional such as:

- Yuko Hara, PhD, director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery

- Michael Merzenich, PhD, professor emeritus at University of California San Francisco

- Montero-Odasso, one of the Synergic study authors and team leader at the Canadian Consortium on Neurodegeneration in Aging, and team co-leader at the Ontario Neurodegenerative Research Initiative

and,

- Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ.

Not surprisingly, in a strong consensus agreement, the above named leaders of their respective fields of study, opined that engagement in mentally stimulating such as number and word puzzles, such as crosswords, cards, or board games may result in improvements in cognition and reduction in dementia risk.

Ditto for regular internet users and socially engaging activities such as dancing, and other exercise activities and such as yoga and swimming.

The point being that apart from more formal brain training programs there is a wealth of strong evidence that links mental and social activities to building a cognitive reserve of new brain connections (synapses) and neural pathways (neuroplasticity)* that significantly improves quality of life measures, and builds a better brain (neurogenesis) as you age and one that is more resilient against cognitive decline in later years.

Think ahead!

*Neuroplasticity, also known as brain plasticity, refers to the brain’s capacity for adaptive change.

Brain plasticity is reflected in the brain’s ability to integrate change
associated with learning, organize that experience, and form new neural connections and pathways that supports and enables that process.

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Does 'Brain Training' Really Improve Cognition?

www.medscape.com

Some companies claimed that engaging in "brain games" can improve cognition or stave off cognitive decline. What's the evidence and do crosswords and Sudoku count?