Promising protein biomarkers in the early diagnosis of Alzheimer's disease

Metab Brain Dis. 2022 Aug;37(6):1727-1744. doi: 10.1007/s11011-021-00847-9. Epub 2022 Jan 11.

Abstract

Alzheimer's disease (AD) is an insidious, multifactorial disease that involves the devastation of neurons leading to cognitive impairments. Alzheimer's have compounded pathologies of diverse nature, including proteins as one important factor along with mutated genes and enzymes. Although various review articles have proposed biomarkers, still, the statistical importance of proteins is missing. Proteins associated with AD include amyloid precursor protein, glial fibrillary acidic protein, calmodulin-like skin protein, hepatocyte growth factor, matrix Metalloproteinase-2. These proteins play a crucial role in the AD hypothesis which includes the tau hypothesis, amyloid-beta (Aβ) hypothesis, cholinergic neuron damage, etc. The present review highlights the role of major proteins and their physiological functions in the early diagnosis of AD. Altered protein expression results in cognitive impairment, synaptic dysfunction, neuronal degradation, and memory loss. On the medicinal ground, efforts of making anti-amyloid, anti-tau, anti-inflammatory treatments are on the peak, having these proteins as putative targets. Few proteins, e.g., Amyloid precursor protein results in the formation of non-soluble sticky Aβ40 and Aβ42 monomers that, over time, aggregate into plaques in the cortical and limbic brain areas and neurogranin is believed to regulate calcium-mediated signaling pathways and thus modulating synaptic plasticity are few putative and potential forthcoming targets for developing effective anti-AD therapies. These proteins may help to diagnose the disease early, bode well for the successful discovery and development of therapeutic and preventative regimens for this devasting public health problem.

Keywords: Alzheimer’s disease; Biomarkers; Diagnosis; Neurodegeneration; Proteins.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Biomarkers
  • Calcium-Binding Proteins
  • Early Diagnosis
  • Glial Fibrillary Acidic Protein
  • Hepatocyte Growth Factor
  • Humans
  • Matrix Metalloproteinase 2
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • CALML5 protein, human
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • HGF protein, human
  • tau Proteins
  • Hepatocyte Growth Factor
  • MMP2 protein, human
  • Matrix Metalloproteinase 2