female researcher pipetting samples

Fla. — Despite decades of scientific scrutiny, Alzheimer’s

researchers have yet to work out its cause or
Understanding what underlies its three distinct subtypes is thought to
be a promising new research avenue.

In a new study in JAMA
Neurology, a team of neuroscientists at Mayo Clinic in

led by Melissa Murray,
examined a key region of the brain and found that patterns of Alzheimer’s-related
damage differed by subtype and age of onset.

The researchers say these observations could have important treatment implications.

“Alzheimer’s affects people in different ways,” says Dr. Murray. “If we learn why, it will help us untangle the mysteries of this disease. We should not continue to think of it as a single entity.”

Dr. Murray, and colleagues from Mayo Clinic and Mount Sinai Medical Center, examined brain tissue donated by over 1,000 deceased Alzheimer’s patients. They focused on an area referred to as the cholinergic hub, which is the target of the only therapies known to effectively manage symptoms in some Alzheimer’s patients. The investigators looked at a main feature of the disease: neurofibrillary tangles, abnormal protein accumulations that disrupt a neuron’s transport system. They observed two interesting patterns.

First, they saw
more severe signs of disease in patients with the “hippocampal-sparing”
subtype of Alzheimer’s. Whereas the typical Alzheimer’s subtype affects the
hippocampus — the brain’s memory center — the hippocampal-sparing subtype mainly
affects the cortex, an area of the brain responsible for thoughts and actions.
Thus, Alzheimer’s patients with this subtype may have symptoms related to
behavior, language or visual disturbances rather than memory loss.

Second, Dr.
Murray and her team observed more Alzheimer’s-related damage in patients with young-onset
Alzheimer’s — presenting with symptoms prior to age 65 — compared to those
whose symptoms arose later in life.

Based on these observations, the researchers believe that available therapies will be most effective for people with this Alzheimer’s subtype and in patients with young-onset form of the disease. As a next step, the researchers hope to test this hypothesis on living patients.

Meanwhile, Dr.
Murray emphasizes the importance of striving for diagnostic accuracy. The
hippocampal-sparing subtype is thought to account for over 10% of Alzheimer’s
cases, but it’s often misdiagnosed due to its younger onset and atypical
symptoms, she says. Cognitive decline can happen quickly for these patients,
making a correct initial diagnosis especially important.

example, our findings suggest that when a younger patient presents with
personality symptoms that may ordinarily point to frontotemporal
the clinician could consider whether a test for Alzheimer’s
biomarkers or other scans
are warranted,” says Dr. Murray.

As her team works
to help future patients, Dr. Murray acknowledges with gratitude the late
Alzheimer’s patients who donated their tissues to the brain bank at Mayo
Clinic in Florida. The facility contains over 7,000 specimens that enable
scientists to better understand neurodegenerative disorders. “Our research
is possible because of the kindness of
Dr. Murray says.

Other researchers
involved in this study are Fadi Hanna Al-Shaikh, the lead author; Julia Crook,
Ph.D.; Elizabeth Lesser; Jolien Schaeverbeke, Ph.D.; Kelly Hinkle; Owen Ross, Ph.D.; Nilufer Taner,
M.D., Ph.D.
Otto Pedraza,
Dennis Dickson,
and Neill Graff-Radford,
— all of Mayo Clinic — as well as Ranjan Duara, M.D., of Mount Sinai Medical

This research
was supported by the National Institute on Aging, the Florida Department of
Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, the
Gerstner Family Career Development Award, and the Alzheimer’s Association.


About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news and An Inside Look at Mayo Clinic for more information about Mayo.

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