Six studies on dementia

The loss of deep non rapid eye movement (non-REM) sleep in Alzheimer's disease (AD) is more than just a symptom - it may actively contribute to disease progression. A recent study led by Ksenia Kastenenka, PhD, tested whether an existing FDA approved sleep drug could be repurposed to restore healthy sleep rhythms in AD patients.

The team identified the sedative zolpidem (Ambien) as a promising candidate due to its ability to enhance inhibitory (calming) brain signaling and tested it in mouse models of early-stage AD.

They found that zolpidem restored deep non REM sleep and its associated slow wave brain rhythms, reduced amyloid plaque burden and selectively improved sleep-dependent contextual memory - all without detectable adverse effects. Read more Open external link in a new window .

One of the key features of Alzheimer's disease is the buildup of sticky clumps or plaques of a protein called amyloid beta in the brain. Amyloid beta is created when a larger protein, called amyloid precursor protein (APP), is broken down inside cells.

Scientists have traditionally focused strategies to remove these plaques after they form, but a recent study suggests there may be an opportunity to intervene much earlier.

In a collaboration with researchers from Yale University, Mass General Brigham investigators Dmitry Prokopenko, PhD Open external link in a new window , and Can (Martin) Zhang, MD, PhD Open external link in a new window , found that a protein called GBF1 helps control how APP moves and is processed inside brain cells.

Finding ways to detect and diagnose AD at the earliest-and most treatable-stages of the disease is a major goal in neurology.

In a recent study, a research team led by Hyun-Sik Yang, MD Open external link in a new window , and Jasmeer Chhatwal, MD, PhD Open external link in a new window , tested whether a simple blood test measuring levels of p-tau217, an AD biomarker, could aid in the early identification of AD patients even before signs appear on brain scans or through memory issues.

The team followed a cohort of cognitively normal adults for eight years.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is an increasingly recognized dementia subtype that often contributes to memory loss in older adults. Currently, it can only be definitively diagnosed after death.

A recent study led by Jijang Wang, PhD Open external link in a new window , and Hyun-Sik Yang, MD Open external link in a new window (pictured above), explored whether a blood test measuring levels of TDP-43 could enable advanced LATE-NC to be diagnosed during life.

TDP-43 is a protein that normally helps cells function properly. In some neurodegenerative diseases such as LATE-NC, however, it becomes abnormal, clumps together and accumulates in the brain. Read more Open external link in a new window .

In another recent study, a research team led by Ella Boberg, PhD, David Walt, PhD Open external link in a new window (pictured at top), and Andrew Stern, MD, PhD Open external link in a new window , tested whether a new, ultrasensitive digital "seed amplification" assay could detect and measure abnormal clumps of TDP-43 in cerebrospinal fluid samples of patients with a form of neurodegenerative disease called frontotemporal lobar dementia with TPD-43 inclusions (FTLD-TDP).

Although early in the development cycle, the team demonstrated that the test was able to distinguish between healthy individuals and those with FTLD-TDP, as well as show that higher levels of TDP-43 "seeds" were linked to more severe disease. These findings highlight the test's potential for detecting and monitoring this condition. Read more.

Most cases of ALS (amyotrophic lateral sclerosis) and frontotemporal dementia (FTD) are not inherited from a parent. In fact, about 90% to 95% of cases occur in people with no known family history of the disease. This has led researchers to ask an important question: What causes these seemingly random cases?

A recent research study suggests that some answers may lie in somatic mutations - genetic changes that occur during a person's lifetime rather than being inherited from their parents. You can think of them as "typos" that appear in the DNA of certain cells as we age.

To investigate, a collaborative research team co-led by Mass General Brigham's Clotilde Lagier-Tourenne, MD, PhD Open external link in a new window , with Eunjung Alice Lee, PhD, and Christopher Walsh, MD, PhD at Boston Children's Hospital, examined brain and spinal cord tissue from hundreds of people with ALS or FTD. They searched for rare mutations in genes known to be linked to neurodegenerative diseases. The team found that a small number of patients had potentially harmful mutations that were present in only a subset of cells and were often limited to the parts of the brain or spinal cord most affected by disease.

In other words, these individuals may not have been born with a disease-causing mutation. Instead, the mutation appears to have developed during embryonic development or later in life in a small group of cells. Over time, those altered cells may have triggered damage that eventually spread and contributed to ALS or FTD. Read more Open external link in a new window .