The progressive dementia of Alzheimer’s disease affects some 35 million people worldwide and is expected to affect 115 million by 2050, yet currently it is not possible to detect the disease before it has caused loss of memory and function. Even then, the tests available are invasive and/or expensive.
The quest to develop a simple blood test for Alzheimer’s is therefore top priority. As ISRAEL21c reported in December last year, the Israeli company NeuroQuest is working with the University of California-San Diego on clinical validation trials of its blood test for very early diagnosis of Alzheimer’s, based on award-winning research led by Prof. Michal Schwartz of the Weizmann Institute of Science in Rehovot.
Now, researchers from three Israeli institutions –Tel Aviv University, Technion and Rambam Medical Center in Haifa — and from Harvard University have published a study in the Journal of Alzheimer’s Disease that proposes testing a novel biomarker in the blood for cognitive aging and Alzheimer’s disease.
The marker, called activity-dependent neuroprotective protein (ADNP), is essential for brain formation and cognitive function.
“This study has provided the basis to detect this biomarker in routine, non-invasive blood tests, and it is known that early intervention is invaluable to Alzheimer’s patients,” said Prof. Illana Gozes, lead researcher.
“We are now planning to take these preliminary findings forward into clinical trials — to create a pre-Alzheimer’s test that will help to tailor potential preventative treatments.”
Gozes holds Tel Aviv University’s Lily and Avraham Gildor Chair for the Investigation of Growth Factors and formerly directed the Adams Super Center for Brain Studies at TAU’s Sackler Faculty of Medicine. She has investigated treatment approaches to Alzheimer’s disease and schizophrenia, as well as a possible link between autism and Alzheimer’s.
ADNP was discovered in Gozes’ lab 15 years ago. “Our study is the first to assess ADNP in elderly individuals at risk for Alzheimer’s disease, and its results open the door for further validation in larger, more informative studies,” she says.
The study had two cohorts, one in the Boston area and one in the Haifa area. Both clearly showed a link between ADNP levels and dementia, but in different ways.
The 40 US subjects were healthy elderly people participating in the Harvard Aging Brain Study. Whole blood samples were analyzed for ADNP levels, and the subjects also took IQ tests.
Results for the US cohort revealed that high levels of serum ADNP correlated with a high IQ score, Gozes tells ISRAEL21c.
In Israel, the study involved 15 patients from 60 to 84 years old with mild cognitive impairment, 17 patients with Alzheimer’s dementia and 11 cognitively normal elderly individuals.
At the Cognitive Neurology Institute at the Rambam Health Care Campus in Haifa, blood samples from this cohort were separated into lymphocytes (white blood cells) and plasma.
Among those with mild cognitive impairment and dementia, researchers saw a dramatic increase in the ADNP gene-activating “messenger RNA” of the lymphocytes, indicating that the mRNA were trying to compensate for low serum ADNP levels.
“ADNP levels in blood may reflect what is going on in the brain, though we need to do further comparisons to get a good picture,” says Gozes. “We can say with certainty that if mRNA is very high in the lymphocytes, it means the patient is not in a good position, and if the ADNP level in the serum goes down it correlates to declining cognitive function.”
She adds that another research group outside Israel has previously observed that out of the entire spectrum of proteins, ADNP is the only one that decreases in Alzheimer patients. In addition, it has been observed that ADNP is frequently mutated in children on the autism spectrum.
“A blood test for ADNP can tell us what is happening in the brain and we need to refine our technology to use it,” she says. “This is something I’m trying to do.”
The study was conducted by TAU doctoral student Anna Malishkevich and spearheaded by Dr. Gad Marshall, Dr. Aaron Schultz and Prof. Reisa Sperling of Harvard Medical School, and Prof. Judith Aharon-Peretz of Rambam Medical Center/Technion-Israel Institute of Technology.
A separate study from Gozes’ lab has found a clear difference in ADNP’s effect on male and female mice.
“There may be a gender difference in the way certain nerves behave and the way the nerve cells communicate. ADNP is involved in this process,” she said. “There are differences between the way men and women react to their environments, and differences at the molecular level may indicate that indeed there are differences between the very way men and women think.”
Results of the study recently were published in the journal Molecular Psychiatry.