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

J Alzheimers Dis. 2016;50(1):249-60. doi: 10.3233/JAD-150799.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / metabolism
  • Chi-Square Distribution
  • Cognitive Dysfunction / blood
  • Cohort Studies
  • Female
  • Homeodomain Proteins / blood*
  • Humans
  • Independent Living
  • Intelligence / physiology*
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Nerve Tissue Proteins / blood*
  • Peptide Fragments / cerebrospinal fluid
  • RNA, Messenger / metabolism
  • tau Proteins / cerebrospinal fluid


  • ADNP protein, human
  • Amyloid beta-Peptides
  • Biomarkers
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (1-42)
  • tau Proteins