Heart Amyloid May Precede Alzheimer’s Symptoms; Brain Study Maps Disease Drivers
A clinical study explores whether echocardiography can detect heart amyloid as an early sign of Alzheimer’s, while laboratory research maps a biphasic gene expression cascade in the brain that identifies new therapeutic targets.
Two new studies offer complementary insights into Alzheimer’s disease: one reveals that amyloid deposits in the heart could enable earlier diagnosis, while the other maps a biphasic molecular cascade in the brain that pinpoints potential therapeutic targets.
Researchers at the Medical University of South Carolina’s del Monte Lab previously discovered that the plaques and tangles characteristic of Alzheimer’s brain pathology also appear in the hearts of people with cardiomyopathy and heart failure. Building on this, a new study aims to find biological markers for earlier detection of both brain and heart disease. The study enrolls three groups: people with heart failure with preserved ejection fraction, people with Alzheimer’s disease, and healthy controls. Participants provide blood and urine samples and undergo physical exams, cognitive tests, electrocardiograms, and echocardiograms. The work, supported by an anonymous donation, will compare echocardiography to PET imaging for diagnosing amyloid in the heart and, potentially, the brain.
“We could diagnose Alzheimer’s ahead of time with an echocardiography,” said del Monte. Mouse models suggest that amyloid accumulations may appear in the heart before the brain, raising the possibility of predicting Alzheimer’s before cognitive symptoms emerge. The study involves two initial visits with four-year and eight-year follow-ups.
Separately, del Monte’s team is developing experimental antibodies to clear plaques in heart failure; one patented antibody reduced plaques and improved cardiac function in lab tests, though side effects have led to work on additional candidates. The long-term vision includes a hybrid heart/brain clinic where neurologists, a cardiologist, and other specialists collaborate on patient care.
In a study published in Molecular Psychiatry, researchers at Baylor College of Medicine and the Duncan Neurological Research Institute integrated postmortem human brain gene expression data with fruit fly experiments to untangle cause-and-effect events leading to neurodegeneration. The AMP-AD consortium analyzed approximately 2,000 brain tissue samples and identified 30 Alzheimer’s-associated gene expression networks, especially those involved in immune and synaptic functions.
The researchers tested 344 genes in fruit flies. Activating immune response genes—whose expression is elevated in Alzheimer’s brains—promoted neurodegeneration, while silencing synaptic genes—whose expression is reduced in the disease—actually protected brain cells. “Our results suggest that the reduced expression of synaptic genes may in fact represent a compensatory response to the damaging brain cell hyperactivity,” said corresponding author Dr. Joshua Shulman.
Based on these findings, the team proposes a biphasic model: early in Alzheimer’s, amyloid plaques trigger an increase in synaptic genes, making brain cells hyperactive and contributing to damage. Later, tau tangles appear to reduce the expression of these same genes as a protective response, but the compensation is insufficient to halt cognitive decline. The results highlight specific driver genes and pathways that may serve as targets for future therapies.