Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.
Highlights
Alzheimer’s disease (AD) represents the most common form of dementia in the elderly population worldwide, accounting for up to 80% of all diagnoses [1]
Increasing efforts phosphorylated tau at threonine 181 (p-tau) and tau positron emission tomography (PET) ligand binding, whereas group N includes have been made in recent years to detect biomarkers in more accessible biological matrices; elevated cerebrospinal fluid (CSF) total tau (t-tau), fluorodeoxyglucose (FDG)-PET hypometabolism and atrophy on in this review we discuss the clinical relevance of emerging candidate biomarkers in CSF and in other promising alternative non-invasive biological fluids as well as novel approaches in “dry” biomarkers like neuroimaging or neurophysiological techniques
Task-activated functional MRI (fMRI) was used in several studies and resulted in a number of observations: mild AD cases have a decrease in hippocampal activity similar to more impaired mild cognitive impairment (MCI) patients [211]; the extent of hippocampal hyperactivation at baseline predicted cognitive decline as measured by the CDR-SB scores over four years after scanning [212]; the hyperactivation is specific to the DG/CA3 subregions of the hippocampus [213]
Summary
Alzheimer’s disease (AD) represents the most common form of dementia in the elderly population worldwide, accounting for up to 80% of all diagnoses [1]. The rare early-onset forms of AD affect individuals under 65 years of age and show an mutations in one of the known genes, namely PSEN1, PSEN2 and APP, encoding the presenilin-1, autosomal dominant pattern of inheritance, generally presenting a positive family history. The lack of success of disease-modifying in past clinical trials designed on enrolled participants with mild-to-moderate AD or with no Aβ therapy may be partially explained by the complex etiology in its pathophysiology and the pathology [10] In this regard, a biomarker holds promise for enabling more effective drug development limitations in past clinical trials designed on enrolled participants with mild-to-moderate AD or in AD and establishing a more personalized medicine approach [11]. Increasing efforts phosphorylated tau at threonine 181 (p-tau) and tau PET ligand binding, whereas group N includes have been made in recent years to detect biomarkers in more accessible biological matrices; elevated CSF total tau (t-tau), fluorodeoxyglucose (FDG)-PET hypometabolism and atrophy on in this review we discuss the clinical relevance of emerging candidate biomarkers in CSF and in other promising alternative non-invasive biological fluids as well as novel approaches in “dry” biomarkers like neuroimaging or neurophysiological techniques
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