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Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disorder with a significant global impact on public health. The emergence of atypical clinical phenotypes challenges traditional diagnostic approaches, necessitating a deeper exploration of biomarkers for accurate identification. The US Food and Drug Administration (FDA) classification of biomarkers and their integration into different stages of AD provide a structured framework for their application in research and clinical settings. Within the context of AD drug development, biomarkers are essential for participant selection, target engagement evaluation, and assessment of pathological hallmarks, including Aβ and tau protein abnormalities. The incorporation of nanoparticles with a biodegradable approach introduces innovative strategies to address the complexities of AD. This paper extensively discusses biomarkers associated with synaptic dysfunction, neuroinflammation, and glial activation, recognizing their significance in elucidating disease mechanisms. Common pathologies such as synuclein and TDP‐43 further underscore the multifaceted nature of AD. Current biomarkers for AD diagnosis, encompassing cerebral spinal fluid (CSF) biomarkers and various imaging modalities, reflect the ongoing efforts to enhance early detection and monitoring. Intriguingly, novel biomarkers continue to emerge, offering promising avenues for improved understanding and intervention. Current review provides a comprehensive survey of biomarkers for AD, elucidating their diverse roles across different aspects of the disease. By highlighting their contributions to diagnosis, drug development, and mechanistic insights, this overview underscores the importance of biomarker research in the pursuit of effective AD management and treatment strategies. [ABSTRACT FROM AUTHOR]