Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer’s disease

ABSTRACT

Introduction: Synaptic dysfunction and degeneration are early fundamental pathophysiological characteristics of Alzheimer’s disease (AD). In addition, synaptic depletion closely correlates with clinical disease severity. Biomarkers that may track synaptic dysfunction in AD are eagerly awaited.

Areas covered: Here, we reviewed the significance of the post-synaptic protein neurogranin – particularly enriched in dendritic spines – as a biomarker of early synaptic dysfunction in AD. We also examined its role as a marker to predict disease progression.

Expert commentary: Current evidence indicates that neurogranin may serve as a mechanism-of-action biomarker aiding the in vivo investigation of AD-related pathophysiological pathways. Its use may support the development of targeted therapeutic interventions tailored to the individual patient, i.e. ‘molecularly’ targeted therapies, according to the evolving precision medicine paradigm.

KEYWORDS:

• Alzheimer’s disease
• synaptic dysfunction
• amyloid beta
• tau protein
• neurogranin
• biomarker
• cerebrospinal fluid
• pathophysiology
• early diagnosis
• precision medicine

Declaration of interest

S. Lista has received lecture honoraria from Roche. H. Hampel is supported by the AXA Research Fund, the Fondation Université Pierre et Marie Curie and the ‘Fondation pour la Recherche sur Alzheimer’, Paris, France. The research leading to these results has received funding from the program ‘Investissements d’avenir’ ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). He serves as Senior Associate Editor for the journal Alzheimer’s & Dementia^®; he has been a scientific consultant and/or speaker and/or attended scientific advisory boards of Axovant, Anavex, Eli Lilly and company, GE Healthcare, Cytox, Jung Diagnostics, Roche, Biogen Idec, Takeda Zinfandel, Oryzon Genomics; and receives research support from the Association for Alzheimer Research (Paris), Pierre and Marie Curie University (Paris), Pfizer & Avid (paid to institution); and has patents as co-inventor, but received no royalties:

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The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.