Journal: Current Alzheimer Research
Guest editor(s):Dr. Jolanta Dorszewska

Introduction

Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder professional activity, social functioning, and performing daily activities. The most common types of dementia are Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Vascular dementia (VaD) and frontotemporal dementia (FTD) are also distinguished. The risk factors for dementia include age, low level of education, hypertension, and other vascular factors. Even after a detailed history, examination, routine laboratory testing, and brain imaging, the cause of dementia sometimes remains unclear. Research is currently underway to develop tests for early detection of dementia. Studies have shown that the ratio of amyloid-β (Aβ) peptides (Aβ42/Aβ40) and plasma concentration of phosphorylated tau isoforms can identify individuals with AD brain pathology. Blood tests may allow for much wider use of AD biomarkers in the assessment of patients with cognitive disorders. Currently, the cause of dementia is also sought among genetic factors. Variants in both causative (APP, PSEN1, PSEN2) and risk of dementia disease apolipoprotein E (APOE) genes can lead to the formation of pathological proteins. Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 direct levels of Aβ42 independently of Aβ pathology remains unknown. The last 10 years have seen a huge increase in biomarker studies within FTD. However, specific markers identifying primary tauopathies or proteinopathies of TDP-43 are still lacking. In patients with FTD clinical trials on specific genetic forms of FTD, measurements of progranulin and dipeptide protein repeats are also underway. Moreover, only one-third of DLB patients are correctly diagnosed due to the clinical similarity mainly with AD. The importance of alpha-synuclein tests in DLB, especially those that do not seem to be directly related to synucleinopathy, is now being highlighted and may be important in the differential diagnosis between AD and DLB. In the future biomarkers may augment the routine dementia evaluation and improve early diagnosis and therapy.

Keywords

biomarker, AD, DLB, FTD, VaD, PDD, dementia