Potential Protein Blood-based Biomarkers in Different Types of Dementia: A Therapeutic Overview.

Biomarkers capable of identifying and distinguishing types of dementia, such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (LBD), and frontotemporal dementia (FTD), have become increasingly relentless. Studies on possible biomarker proteins in the blood that can help formulate new diagnostic proposals and therapeutic visions of different types of dementia are needed. However, due to several limitations of these biomarkers, especially in discerning dementia, their clinical applications are still undetermined. Thus, updating biomarker blood proteins that can help in the diagnosis and discrimination of these main dementia conditions is essential to enable new pharmacological and clinical management strategies with specificities for each type of dementia. This paper aimed to review the literature concerning protein bloodbased AD and non-AD biomarkers as new pharmacological targets and/or therapeutic strategies. Recent findings related to protein-based AD, PDD, LBD, and FTD biomarkers are focused on in this review. Protein biomarkers are classified according to the pathophysiology of the dementia types. The diagnosis and distinction of dementia through protein biomarkers is still a challenge. The lack of exclusive biomarkers for each type of dementia highlights the need for further studies in this field. Only after this, blood biomarkers may have a valid use in clinical practice as they are promising to help in the diagnosis and in the differentiation of diseases.

Blood-based Biomarkers of Alzheimer's Disease: The Long and Winding Road.

BACKGROUND: Blood-based biomarkers can be very useful in formulating new diagnostic and treatment proposals in the field of dementia, especially in Alzheimer's disease (AD). However, due to the influence of several factors on the reproducibility and reliability of these markers, their clinical use is still very uncertain. Thus, up-to-date knowledge about the main blood biomarkers that are currently being studied is extremely important in order to discover clinically useful and applicable tools, which could also be used as novel pharmacological strategies for the AD treatment. METHODS: A narrative review was performed based on the current candidates of blood-based biomarkers for AD to show the main results from different studies, focusing on their clinical applicability and association with AD pathogenesis. OBJECTIVE: The aim of this paper was to carry out a literature review on the major blood-based biomarkers for AD, connecting them with the pathophysiology of the disease. RESULTS: Recent advances in the search of blood-based AD biomarkers were summarized in this review. The biomarkers were classified according to the topics related to the main hallmarks of the disease such as inflammation, amyloid, and tau deposition, synaptic degeneration and oxidative stress. Moreover, molecules involved in the regulation of proteins related to these hallmarks were described, such as non-coding RNAs, neurotrophins, growth factors and metabolites. Cells or cellular components with the potential to be considered as blood-based AD biomarkers were described in a separate topic. CONCLUSION: A series of limitations undermine new discoveries on blood-based AD biomarkers. The lack of reproducibility of findings due to the small size and heterogeneity of the study population, different analytical methods and other assay conditions make longitudinal studies necessary in this field to validate these structures, especially when considering a clinical evaluation that includes a broad panel of these potential and promising blood-based biomarkers.