Abstract
Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection.
Highlights
We have divided the below presentation in biomarkers that are specific of Alzheimer’s disease (AD), where their appropriate combination in biological fluids defines the disease, from biomarkers that are representative of neurodegeneration or associated pathology, such as synaptic and neuronal loss, inflammation, vascular disease and others
While it is possible to detect a reduction of the Aβ42/40 ratio in plasma in AD vs. control subjects, plasma reduction only totals about 15%, while in cerebrospinal fluid (CSF) we can see as much as 50% reduction [115,176]
Several studies have assessed the use of isolated biomarkers vs. their combinations to predict diagnosis of AD, or progression of Mild cognitive impairment (MCI) to AD
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by progressive cognitive impairment, affecting the domains of memory, speech, praxis, awareness and executive function, representing a decline from the prior functional state, with a relentless course [1] It is the most common cause of dementia. It is speculated that Aβ accumulates first; this is followed by the hyperphosphorylation, conformational changes and aggregation of tau; neuronal loss ensues The link between these three features is, to some degree, still loose. Lack of familiarity with alternative diagnoses, leads to overdiagnosis of AD in more than 25% of the cases, where potentially curable conditions are instead the underlying cause of the cognitive and functional decline [53,54,55,56]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
