Tel Aviv University, Harvard, and Technion team report that a routine blood test could reveal Alzheimer’s risk and relate to IQ
Diagnosing Alzheimer’s disease today often requires lengthy cognitive evaluations, expensive brain imaging and, in some cases, invasive testing of cerebrospinal fluid. These procedures can be time-consuming, costly and sometimes subjective. A new collaborative study from researchers at Tel Aviv University, the Technion’s Rambam Medical Center, and Harvard University points to a simpler, less invasive approach: measuring the activity-dependent neuroprotective protein (ADNP) in blood as a potential biomarker for cognitive aging and Alzheimer’s disease.
The study, published in the Journal of Alzheimer’s Disease, shows that ADNP levels measured in plasma, serum and white blood cell RNA correlate with clinical stage—from cognitively normal older adults through mild cognitive impairment (MCI) to Alzheimer’s dementia—and with premorbid intelligence. The research team included Prof. Illana Gozes of Tel Aviv University, TAU PhD student Anna Malishkevich, Dr. Gad Marshall and Dr. Aaron Schultz, Prof. Reisa Sperling of Harvard, and Prof. Judith Aharon-Peretz of Rambam Medical Center at the Technion.
Promising step toward earlier intervention
In a cross-sectional analysis, the investigators examined blood samples from 42 participants at Rambam Medical Center, including healthy older adults, individuals with MCI and patients with Alzheimer’s disease. They measured ADNP expression in blood cells and compared protein levels in plasma and serum. The results showed a pattern: ADNP mRNA levels in white blood cells rose significantly in subjects with cognitive impairment, while serum and plasma ADNP levels also varied by clinical stage. Importantly, higher serum ADNP was associated with greater premorbid intelligence among cognitively normal older adults.
“Detecting this biomarker in routine, non-invasive blood tests could be a major advance, because early intervention is invaluable for people at risk of Alzheimer’s,” said Prof. Gozes. The team is planning larger clinical trials to validate these preliminary findings and to develop a pre-Alzheimer’s screening test that could guide personalized preventive strategies.
Builds on prior molecular research
The study extends Prof. Gozes’ earlier work on neuronal plasticity and neuroprotection, including the discovery of ADNP and related proteins that support communication between neurons and glial cells. In this clinical study, the investigators found a notable relationship between ADNP measures in blood and established Alzheimer’s pathology: greater cortical amyloid burden was associated with lower ADNP and ADNP2 mRNA levels, while ADNP mRNA increased in later clinical stages. ADNP2 transcripts tracked closely with ADNP, especially in lymphocytes from participants with Alzheimer’s dementia.
These complex patterns suggest that ADNP blood levels change across the course of disease: in some mild cases serum ADNP may be reduced, while in more advanced stages ADNP mRNA in white blood cells can rise dramatically. The researchers note that such increases may be compensatory or could reflect disease-related dysregulation, and that further study is needed to clarify these mechanisms.
“We observed a clear association between ADNP levels in the blood and amyloid plaques in the brain,” Prof. Gozes said. “This is the first study to evaluate blood-borne ADNP in elderly individuals at risk for Alzheimer’s, and the findings support pursuing larger, more definitive studies to determine whether ADNP can predict cognitive decline and disease progression.”
Source: AFTAU
Image Source: Image adapted from the AFTAU press release
Original Research: Malishkevich, Anna; Marshall, Gad A.; Schultz, Aaron P.; Sperling, Reisa A.; Aharon-Peretz, Judith; and Gozes, Illana. Study published in the Journal of Alzheimer’s Disease (online February 2016). The paper is titled “Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer’s Disease Biomarkers.”
Abstract (summary)
ADNP is essential for brain development and linked to cognitive functions. This study found that blood-borne ADNP and its paralog ADNP2 correlate with premorbid intelligence, Alzheimer’s pathology and clinical stage. After adjusting for age, higher premorbid intelligence associated with greater serum ADNP, while greater cortical amyloid correlated with lower ADNP and ADNP2 mRNA. ADNP mRNA levels rose significantly from MCI to Alzheimer’s dementia, and ADNP plasma/serum and lymphocyte mRNA measurements discriminated among cognitively normal elderly, MCI and Alzheimer’s dementia groups. These findings suggest that measuring ADNP in blood could advance screening and monitoring for Alzheimer’s disease.