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Table 2 Main pathway and biomarkers AD related cited in this review

From: The "Alzheimer's disease signature": potential perspectives for novel biomarkers

Pathway

Biomarker

Potential association with AD

Signal transduction

GSK3β

GSK3β integrates a variety of intracellular and extracellular pathways and appears to be increased in the AD brain. GSK3β is regulated by phosphorylation and is the major tau kinases.

 

CDK5

Cdk5 plays a role in processes of neural development, synaptic signalling, learning and can influence tau phosphorylation indirectly via regulation of GSK3β.

 

ERK2

The phosphorylation of tau by ERK2 induces tau to acquire biochemical properties of AD. ERK2 was detected in neurofibrillary tangles.

 

DYRK1A

Dyrk1A is abnormally expressed in AD and recently it has been found to be associated with neurofibrillary tangles in sporadic AD.

 

PKC

PKC has been implicated in memory mechanisms and is also involved in the processing of APP. The activators of PKC lead to increased processing of APP by the α-secretase pathway.

 

VLP-1

Visinin-like protein 1 concentration is significantly altered in the CSF of AD patients and ia is associated with fibrillar tangles in AD brains.

Oxidative stress

F2-isoprostanes

Incresed levels of F2-isoprostanes are found in AD plasma and CSF.

Inflammation

Interleukins

Interleukins are consistently detected in the brains of AD and polymorphisms are implicated in AD. The activity in AD contributes to synaptic dysfunction and loss, and later, neuronal death.

 

TNF-α

TNF-α has a central role in AD pathogenesis. The levels are increased in CSF and correlated with clinical deterioration.

 

C-reactive protein

C-reactive protein has been found to be associated with AD in histopathological and longitudinal studies. It is associated with increased risk of AD.

 

α-1-antichymotrypsin

α-1-antichymotrypsin participates in the inflammatory cascade of AD and enhances the formation of amyloid-fibrils.

 

α2-macroglobulin

α2-macroglobulin has an important role in AD etiopathology. The main ability is to mediate the clearance and degradation of Aβ.

 

Homocysteine

Hyperhomocysteinaemia is a risk factor for AD and mental decline.

 

ICAM-1

ICAM-1 is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients and seems to be implicated in the process of neuro-degeneration.

 

VCAM-1

Abnormal levels of VCAM-1 levels have been found in individuals with AD as well as other cell adhesion molecules.

Lipid metabolism

Total cholesterol

High concentration of serum cholesterol is associated with increased risk of incident AD.

 

APOE

APOE E2, E3, and E4 alleles alter the likelihood of developing AD and cerebral amyloid angiopathy.