Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD.
Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) Campus, New Delhi, India.|Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India.
Puneet
P
Talwar
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India.
Juhi
J
Sinha
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India.|Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
Sandeep
S
Grover
Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) Campus, New Delhi, India.|Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India.
Chitra
C
Rawat
Institute of Human Behaviour and Allied Sciences (IHBAS), Delhi, India.
Suman
S
Kushwaha
Institute of Human Behaviour and Allied Sciences (IHBAS), Delhi, India.
Rachna
R
Agarwal
Department of Research, Sir Ganga Ram Hospital, New Delhi, India.
Vibha
V
Taneja
Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) Campus, New Delhi, India. ritus@igib.res.in.|Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India. ritus@igib.res.in.
Ritushree
R
Kukreti
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D057890:Epigenomics / Q000379:methods / Q000639:trends; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods / Q000639:trends; D023281:Genomics / Q000379:methods* / Q000639:trends; D006801:Humans; D049490:Systems Biology / Q000379:methods / Q000639:trends*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E
Alzheimer’s disease; Endophenotype; Epigenetics; Etiology; Genome-wide association; Genome-wide expression studies; Genome-wide linkage