Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer’s Disease Biomarkers

Article type: Research Article

Authors: Malishkevich, Anna^a | Marshall, Gad A.^{b; c} | Schultz, Aaron P.^c | Sperling, Reisa A.^{b; c} | Aharon-Peretz, Judith^d | Gozes, Illana^{a; *}

Affiliations: [a] Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Sagol School of Neuroscience & Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel | [b] Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [c] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] Cognitive Neurology Unit, Rambam Medical Center, Haifa, Israel

Correspondence: [*] Correspondence to: Prof. Illana Gozes, PhD, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience & Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv 69978, Israel. Tel.: +972 972 3 640 7240; Fax: +972 3 640 8541; E-mail: [email protected].

Abstract: Biomarkers for Alzheimer’s disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

Keywords: Activity-dependent neuroprotective protein (ADNP), Alzheimer’s disease, amyloid-beta, blood-borne biomarkers, cognitively normal, mild cognitive impairment, premorbid intelligence

DOI: 10.3233/JAD-150799

Journal: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 249-260, 2016