APMI Research Core Objectives
The major objective of the APMI Research Network and Program is to transform Neurology, Psychiatry, and Neuroscience embracing the Precision Medicine paradigm based on complex systems theory using systems biology and systems neurophysiology, “big data” science, and biomarker-guided integrative disease modeling (IDM) for improved detection, classification, and therapy development in Alzheimer’s Disease (AD) and other neurodegenerative diseases.
The definition of AD has been shifted to a clinical-biological construct conferring a crucial diagnostic role to biomarker capable of charting pathomechanistic alterations of AD along its clinical continuum, from preclinical to prodromal dementia stages. An unbiased, clinically agnostic, biomarkers-based classification scheme, the “ATN+” system, has been proposed to classify individuals by the presence of AD pathophysiological hallmarks (brain overaccumulation of both amyloid-β [A] and tau [T] proteins aggregates, and neurodegeneration [N]), regardless to any clinical manifestation. The ATN+ categorization scheme is intended to be flexible and able to integrate novel biomarkers, once they are disclosed and validated, within its existing groups.
The main aims of the APMI Research Program are discovering and developing multimodal biomarkers for risk assessment, screening, progression, diagnosis, prognosis, and staging of AD across the continuum of the disease.
1) biochemical (blood [plasma/serum] & cerebrospinal fluid [CSF]) biomarkers enable to track key molecular pathways and pathomechanistic alterations of AD and other neurodegenerative diseases.
2) genetic - epigenetic profiling can enable the detection and stratification of population cohorts according to genetic risk and or protection factors
3) neurophysiological (EEG, MEG), and structural / functional / metabolic neuroimaging (MRI, DTI, fMRI, PET) methods are essential to predict brain endophenotypes.
Multi-dimensional integrative methods, based on consolidated and emerging Artificial Intelligence-based techniques, allows to investigate the relationship between relevant molecular mechanisms and brain network functional dynamics. Addressing these questions will better approximate the true complexity of brain endophenotypes. Hence, the APMI Research Program aims at untangling whether any specific brain endophenotype is associated with specific (epi)genetic - biological patterns.
The APMI approach is based on the robust translational evidence that AD is a heterogeneous entity characterized by different multiple genetic and biological subsets. In this regard, the implementation of Precision Medicine in AD and other neurodegenerative disorders along the spectrum of the so-called brain proteinopathies with neurodegeneration will result with optimized clinical profiles based on biological and genetic features. This approach will produce better responder rates, particularly in early disease-stage clinical trials, thus providing in the next future substantial benefits to patients suffering from this disease.
The identification of multi-dimensional biological markers will allow the development of targeted translational applications supporting clinicians in providing more efficacious and helpful pharmacological treatments defined as customized (or “tailored”) – that is to say adapted – to the definite profiles of their AD patients.
Following the Precision Medicine approach, the APMI Research Program will focus on AD as a core model of disease where the need to accurately chart all the stages of disease continuum – from preclinical to prodromal to dementia stages – is expected to be crucial for both clinical practice and drug research & development.