Tau as a biomarker of cognitive impairment and neuropsychiatric symptom in Alzheimer's disease

Abstract

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini‐mental state examination and Neuropsychiatric Inventory scales. Tau, Aβ, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two‐sample t ‐tests, and support vector machine algorithms were used to explore the relationship between tau, Aβ, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region‐specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aβ were unique and the regions affected by hypometabolism were widely distributed. Unlike Aβ, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aβ. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aβ (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aβ and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD.

Associations Between Blood-Based Biomarkers and Cognitive and Functional Trajectories Among Participants of the MEMENTO Cohort

“…Unlike tau pathology, which is widely acknowledged for its association with clinical manifestation of AD, cortical amyloid accumulation shows a less robust association with cognitive or functional decline. 39 , 40 In this study, we observed only weak associations between blood-based Aβ42/40 ratio and memory and semantic fluency decline. A recent study similarly failed to evidence an association between plasma Aβ42/40 ratio and global cognitive decline.…”

“…Tau-PET imaging studies have consistently shown a correlation between the accumulation of neurofibrillary tangles and the clinical manifestation and progression of symptoms in AD. 39 , 40 The regional distribution of neurofibrillary tangles corresponds to deficits observed in specific cognitive domains. Recent studies have shown that, even when measured in blood, p-tau is associated with the cognitive manifestations of AD, 17 , 18 , 20 , 41 , 42 independent of confounding factors such as renal function.…”

Evaluating p-tau217 and p-tau231 as Biomarkers for Early Diagnosis and Differentiation of Alzheimer’s Disease: A Narrative Review

“…Interestingly, blood levels of tau and p-tau differ significantly among individuals with cognitive impairments, traumatic brain injury (TBI), or COVID-19. The study by Dang et al [122] emphasizes the significant correlation between tau accumulation and cognitive decline, as well as neuropsychiatric symptoms, showcasing its diagnostic superiority over Aβ for distinguishing AD patients from cognitively normal controls. Notably, tau PET imaging demonstrates greater accuracy than Aβ in this differentiation, with pronounced tau deposition in the inferior temporal lobes strongly associated with the severity of cognitive impairments.…”

Comparative interactome mapping of Tau‐protein in classical and rapidly progressive Alzheimer's disease identifies subtype‐specific pathways

“…AD is a dual proteinopathy (Aβ and Tau pathology). However, the load of misfolded Tau protein (Tau pathology) seems to be the critical factor in determining cognitive decline [18,19]. Like all proteins in a cell, the precise functions and localisation of Tau protein are dependent on its interaction with many other cellular proteins [20,21].…”