Biomarkers in Sporadic and Familial Alzheimer’s Disease

Article type: Research Article

Authors: Lista, Simone^{a; b; *} | O’Bryant, Sid E.^c | Blennow, Kaj^d | Dubois, Bruno^b | Hugon, Jacques^{e; f} | Zetterberg, Henrik^{d; g} | Hampel, Harald^{a; b}

Affiliations: [a] AXA Research Fund & UPMC Chair, Paris, France | [b] Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France | [c] Institute for Aging and Alzheimer’s Disease Research & Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA | [d] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [e] Centre Mémoire de Ressources et de Recherche (CMRR) Paris Nord Ile-de-France, Groupe Hospitalier Saint Louis Lariboisière - Fernand Widal, Université Paris Diderot, Paris 07, Paris, France | [f] Institut du Fer à Moulin (IFM), Inserm UMR_S 839, Paris, France | [g] University College London Institute of Neurology, Queen Square, London, UK

Correspondence: [*] Correspondence to: Simone Lista, PhD, AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Pavillon François Lhermitte, Hôpital de la Pitié-Salpétrière, 47 Boulevard de l’Hôpital, 75651 - Paris, CEDEX 13, France. Tel.: +33 1 42 16 19 25; Fax: +33 1 42 16 75 16; slista@libero.it

Abstract: Most forms of Alzheimer’s disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the “exploratory biomarker discovery arena”, proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

Keywords: Alzheimer’s disease, blood-based biomarkers, cerebrospinal fluid biomarkers, familial Alzheimer’s disease, metabolomics/lipidomics, neuroimaging markers, proteomics, sporadic Alzheimer’s disease, systems biology, temporal ordering of biomarkers

DOI: 10.3233/JAD-143006

Journal: Journal of Alzheimer's Disease, vol. 47, no. 2, pp. 291-317, 2015