Alzheimer’s Research: Progressing towards a tau blood test for Alzheimer’s disease

Alzheimer’s Research UK | July 2020 | Progressing towards a tau blood test for Alzheimer’s disease

• Four new studies presented at the Alzheimer’s Association International Conference (AAIC) and two published papers show that levels of tau, a hallmark protein of Alzheimer’s disease, in the blood could be used to detect the disease
• The research focuses on a specific form of tau, p-tau217
• The new data suggests blood levels of p-tau217 can predict the development of Alzheimer’s disease before symptoms appear, track well with levels of tau in the brain and distinguish Alzheimer’s from other diseases that cause dementia

Researchers from both the US and Europe have presented data that indicates levels of a specific form of tau, one of the hallmark proteins of Alzheimer’s disease, can be measured in blood to detect the disease, even before symptoms appear. 

Full details of the studies are available from Alzheimer’s Research UK

In the news:

The Independent ‘Exciting’ results on blood test that could detect Alzheimer’s 20 years before memory falter

BBC News Alzheimer’s: ‘Promising’ blood test for early stage of disease

The Telegraph Flu jab may reduce risk of dementia by a fifth, study finds

Decreased deep sleep linked to early signs of Alzheimer’s disease

Researchers have uncovered part of the explanation for why poor sleep is linked to Alzheimer’s disease. | via ScienceDaily

Poor sleep is a hallmark of Alzheimer’s disease. People with the disease tend to wake up tired, and their nights become even less refreshing as memory loss and other symptoms worsen. But how and why restless nights are linked to Alzheimer’s disease is not fully understood.

Now, researchers at Washington University School of Medicine in St. Louis may have uncovered part of the explanation. They found that older people who have less slow-wave sleep — the deep sleep needed to consolidate memories and wake up feeling refreshed — have higher levels of the brain protein tau. Elevated tau is a sign of Alzheimer’s disease and has been linked to brain damage and cognitive decline.

The findings, published in Science Translational Medicine, suggest that poor-quality sleep in later life could be a red flag for deteriorating brain health.

Full story at ScienceDaily

Link to research: Lucey BP, et al. | Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease | Science Translational Medicine | Jan. 9, 2019

See also: Lack of deep sleep and more day time naps could be early sign of Alzheimer’s, study suggests | The Independent

Alzheimer’s Society to fund Exeter research into brain inflammation

University of Exeter | November 2018 | Alzheimer’s Society to fund Exeter research into brain inflammation

The Alzheimer’s Society is funding research at the University of Exeter as  part of a three-year project which will investigate the role that infections have in driving inflammation in the brain of someone with Alzheimer’s disease. The researchers have received a £361,000 grant to enable their research in this area. 

Professor Katie Lunnon, Associate Professor of Epigenetics at the University of Exeter Medical School said: “Systemic infections, like pneumonia or a urinary tract infection, are associated with the onset of dementia, a faster rate of cognitive decline, and the increased risk of death in those living with dementia. Understanding the role of inflammation in Alzheimer’s disease is of utmost importance if we are to treat the disease more effectively.” (Source: University of Exeter)

The full story is available from University of Exeter

Sleep Disturbances in Alzheimer’s Disease

Sleep requirements change throughout life. As part of normal aging, sleep generally becomes briefer and fragmented, with older people often having multiple naps throughout the day. In this article, Osman Shabir explains that this may not be the pattern of sleep seen in patients with Alzheimer’s disease and other neurodegenerative conditions, however. | via News Medical

Most patients with Alzheimer’s develop sleep problems which worsen as the disease progresses. Some common sleep disturbances seen in patients with Alzheimer’s are:

• Loss of the ability to stay asleep, despite being able to get to sleep
• Increased sleep latency (duration required to get to sleep is longer)
• Increased agitation before bedtime and throughout the night
• Disorientation upon waking up (in the night, or in the morning)
• Sleepy during the day, whilst being alert during the night (circadian abnormalities)
• Periodic limb movement (PLM) is worsened in around 50% of Alzheimer’s patients
• Shorter duration of both slow-wave-sleep (SWS) and rapid-eye movement sleep (REM) despite the total number of sleep cycles remaining unchanged

The article notes however that not all studies have shown a significant correlation between sleep disruption and Alzheimer’s disease, either in the pre-clinical stage or after symptoms develop. Therefore, not all Alzheimer’s patients suffer from sleep problems, and likewise, not all people suffering from sleep issues in older age necessarily have Alzheimer’s. However, it is now increasingly accepted that sleep loss may indeed be an important risk factor and symptom of Alzheimer’s disease. Whether sleep loss contributes to Alzheimer’s progression, or whether Alzheimer’s causes sleep problems, is yet to be determined.

Full article: Alzheimer’s Disease and sleep disruption | News Medical

How Alzheimer’s disease spreads through the brain

A new computer model maps how misshapen proteins associated with Alzheimer’s and Parkinson’s diseases spread throughout the brain. The work could aid in finding ways to diagnose and treat these neurodegenerative disorders | via Stanford News

For the first time, scientists have developed a computer simulation of how clumps of defective proteins in neurodegenerative diseases like Alzheimer’s spread through the brain, much of the time in stealth mode, over as long as 30 years.

“We hope the ability to model neurodegenerative disorders will inspire better diagnostic tests and, ultimately, treatments to slow down their effects,” said Stanford mechanical engineer Ellen Kuhl, who describes the work in  Physical Review Letters.

Full article at Stanford News

First patient trial will test new approach to treating Alzheimer’s disease

UCL | October 2018 | First patient trial will test new approach to treating Alzheimer’s disease

A new clinical trial that is using a novel approach to the progression of Alzheimer’s disease is being led by UCL researchers in London. The trial known as DESPIAD will study whether a drug that removes a protein from the brain can help patients with Alzheimer’s disease. 

 “After a long struggle for funding of our different approach to possible treatment of Alzheimer’s disease, it is exciting to finally have started the DESPIAD trial, which has been made possible by the NIHR and the Wolfson Foundation. We now hope it can proceed as swiftly as possible,” said Professor Sir Mark Pepys (UCL Medicine), who led the development of the new drug.

Almost all medications tested have been focussed on the abnormal fibrous protein accumulations, known as amyloid plaques and neurofibrillary tangles, which are always present in the brain in Alzheimer’s disease. The drugs have aimed at removing or preventing the formation of these abnormal deposits (Source: UCL).

For the full details of the trial, read the press release from  UCL 

See also:

NIHR | Landmark new trial starts for novel Alzheimer’s disease treatment

Stroke and dementia risk: A systematic review and meta-analysis

Kuźma, Elżbieta et al.| 2018| Stroke and dementia risk: A systematic review and meta-analysis| Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association , Vol. 0 , Issue 0 | https://doi.org/10.1016/j.jalz.2018.06.3061

A new systematic review and meta- analysis is the first to conduct a meta-analysis of the relationship between stroke and all-cause dementia risk. This systematic review and meta-analysis provides evidence that stroke is a strong independent risk factor for dementia. The review is published in Alzheimer & Dementia: The Journal of the Alzheimer’s Association.

Abstract

Introduction

Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk.

Methods

We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers.

Results

We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69. Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke.

Discussion

Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

Read the full article at the Alzheimer’s & Dementia

 

How does alcohol influence the development of Alzheimer’s disease?

Research has found that some of the genes affected by alcohol and inflammation are also implicated in processes that clear amyloid beta — the protein that forms globs of plaques in the brain and which contributes to neuronal damage and the cognitive impairment associated with Alzheimer’s disease | Journal of Neuroinflammation | story via ScienceDaily

Previous studies investigating the effects of alcohol consumption on Alzheimer’s disease have been controversial — some have indicated that alcohol has a protective effect, while others have pointed to a deleterious role for alcohol in the development of this neurocognitive disease. Recent research has suggested that alcohol consumption, and its impact on the immune system and inflammation in the brain, may be the vehicle through which alcohol might exert its influence on the development of Alzheimer’s disease, but no previous studies have directly evaluated which genes are affected by alcohol in cells in the brain involved in protecting against Alzheimer’s disease.

In this study, researchers conducted a cell-based study which suggests that alcohol may impede the clearance of amyloid beta in the brain. Their results are published in the Journal of Neuroinflammation.

Full reference: Kalinin, S. et al | Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis | Journal of Neuroinflammation, 2018; 15 (1)

Rise in Alzheimer’s and dementia deaths

Alzheimer’s and dementia now account for more than one in every 10 deaths in Scotland, double the rate of a decade ago | National Records of Scotland | via BBC News

Data from the National Records of Scotland (NRS) showed a 15.8% increase in deaths from Alzheimer’s in the final three months of 2017 compared with 2016. The number of deaths from dementia also rose by 12.3% over the same period. The NRS said the rise was in part due to more accurate recording of the data.

The figures continue a trend that emerged in data from the second quarter of 2017 and which revealed a 33.4% rise in deaths from Alzheimer’s and dementia.

Full publication Births, Deaths and Other Vital Events – Quarterly Fiqures

 

New research shows where in the brain the earliest signs of Alzheimer’s occur

Researchers have convincingly shown where in the brain the earliest signs of Alzheimer’s occur.  Nature Communications | Story via ScienceDaily

In Alzheimer’s, the initial changes in the brain occur through retention of the protein, ?-amyloid (beta-amyloid). The process begins 10-20 years before the first symptoms become noticeable in the patient.

In Nature Communications, a research team has presented results showing where in the brain the initial accumulation of ?-amyloid occurs.  It is hoped that the discovery could potentially become significant to future Alzheimer’s research while contributing to improved diagnostics.

Full story at ScienceDaily

Link to the research: Palmqvist, S et al. Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nature Communications, 2017; 8 (1)