Explorative and targeted neuroproteomics in Alzheimer's disease

• Review of both explorative and targeted neuroproteomic studies of AD
• Quantitative differences in protein expression between patients with AD and controls
• Quantitation with 2-D gel electrophoresis and mass spectrometry both label and label-free
• Targeted approaches with immunopurification and SRM mass spectrometry
• Results, challenges and limitations of neuroproteomic studies in AD are discussed.

Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other higher brain functions. Neuropathologically, the disease is characterized by accumulation of a 42 amino acid peptide called amyloid β (Aβ42) in extracellular senile plaques, intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Biomarker assays capturing these pathologies have been developed for use on cerebrospinal fluid samples but there are additional molecular pathways that most likely contribute to the neurodegeneration and full clinical expression of AD. One way of learning more about AD pathogenesis is to identify novel biomarkers for these pathways and examine them in longitudinal studies of patients in different stages of the disease. Here, we discuss targeted proteomic approaches to study AD and AD-related pathologies in closer detail and explorative approaches to discover novel pathways that may contribute to the disease.This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.