Alzheimer’s disease

Background

Alzheimer’s disease (AD) is the most common cause of dementia and accounts for 50%-75% of all cases. It has been identified as a protein misfolding disease caused by plaque accumulation of abnormally folded beta amyloid and tau amyloid proteins in the brain.[2] Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (Aβ) which is a fragment from a larger protein called amyloid precursor protein (APP), which is critical to neuron growth, survival and post-injury repair.[3][4] In AD, a proteolysis process causes APP to be divided into smaller fragments [5] which gives rise to fibrils of beta-amyloid  that deposit outside neurons in dense formations known as senile plaques.[1][6]. Exactly how disturbances of production and aggregation of the beta-amyloid peptide gives rise to the pathology of AD is not known.[7][8]

Useful markers for Alzheimer’s disease

• Aβ40 – b-amyloid 1-40
• Aβ42 – b-amyloid 1-42
• ApoE – Apolipoprotein E
• APP – Amyloid precursor protein
• AST – Aspartate aminotransferase
• BACE1 – Beta-secretase 1
• GFAP – Glial fibrillary acidic protein
• NFT – Neurofibrillary tangle
• Tau

For a list of PubMed review on markers for Alzheimer’s disease click here.

References

1. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The Importance of Neuritic Plaques and Tangles to the Development and Evolution of AD. Neurology. 2004;62(11):1984–9..
2. Hashimoto M, Rockenstein E, Crews L, Masliah E. Role of Protein Aggregation in Mitochondrial Dysfunction and Neurodegeneration in Alzheimer’s and Parkinson’s Diseases. Neuromolecular Med.. 2003;4(1–2):21–36.
3. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse Formation and Function is Modulated by the Amyloid Precursor Protein. J. Neurosci.. 2006;26(27):7212–21.
4. Turner PR, O’Connor K, Tate WP, Abraham WC. Roles of Amyloid Precursor Protein and its Fragments in Regulating Neural Activity, Plasticity and Memory. Prog. Neurobiol.. 2003;70(1):1–32.
5. Hooper NM. Roles of Proteolysis and Lipid Rafts in the Processing of the Amyloid Precursor Protein and Prion Protein. Biochem. Soc. Trans.. 2005;33(Pt 2):335–8.
6. Ohnishi S, Takano K. Amyloid Fibrils from the Viewpoint of Protein Folding. Cell. Mol. Life Sci.. 2004;61(5):511–24.
7. Van Broeck B, Van Broeckhoven C, Kumar-Singh S. Current Insights into Molecular Mechanisms of Alzheimer Disease and Their Implications for Therapeutic Approaches.Neurodegener Dis. 2007;4(5):349–65..
8. Huang Y, Mucke L. Alzheimer Mechanisms and Therapeutic strategies. Cell. 2012;148(6):1204-22.