Alzheimer’s Disease: From Differential Diagnosis to Precision Medicine

Alzheimer’s disease (AD) accounts for 50 to 70% of all dementia cases in the elderly worldwide, with no available cure. The differential diagnosis of ‘probable AD’ is currently based on the clinical evaluation of cognitive symptoms and the exclusion of alternative causes of dementia. As a result, AD patients represent a heterogeneous group, with highly variable disease presentation and progression; interpersonal variability has significantly hindered the therapeutic development in the last decade, with the failure of all clinical trials for AD.

The recent development of imaging and fluid biomarkers, as well as the identification of a number of novel genetic risk factors, have revolutionized the landscape of AD, bringing us closer to precise, molecular diagnosis of the disease. However, these tests are still far from clinical practice; even in biomarker-positive individuals, the onset and progression of the disease is highly variable and individual level prediction is still unattained. In this talk I will provide an overview of recent developments in the field of AD with potential implications for precision diagnosis and treatment. In particular, I will propose two emerging themes: new-generation inflammatory biomarkers, and the role of biological sex in phenotypic variability. In addition, I will discuss the aims and structure of the recently launched Alzheimer’s Disease Precision Medicine Initiative. Precision medicine, based on accurate diagnosis, disease target identification and tailored treatment, promises to reshape the AD field.