LITERATURE UPDATE


suggests that blood GFAP levels can be used to detect early-stage AD. In this systematic review and meta- analysis, the authors aimed to evaluate GFAP in peripheral blood as a biomarker for AD and provide an overview of the evidence regarding its utility. This analysis revealed that the GFAP level in the blood was higher in the Aβ-positive group than in the negative groups, and in individuals with AD or mild cognitive impairment (MCI) compared to the healthy controls. Therefore, they believe that the clinical use of blood GFAP measurements has the potential to accelerate the diagnosis and improve the prognosis of AD.


Plasma biomarkers predict Alzheimer’s disease before clinical onset in Chinese cohorts


Cai H, Pang Y, Fu X, Ren Z, Jia L. Nat Commun. 2023 Oct 24; 14 (1): 6747. doi: 10.1038/s41467-023-42596-6.


Plasma amyloid-β (Aβ)42, phosphorylated tau (p-tau)181 and neurofilament light chain (NfL) are promising biomarkers of Alzheimer’s disease (AD). However, whether these biomarkers can predict AD in Chinese populations is yet to be fully explored. This study therefore tested the performance of these plasma biomarkers in 126 participants with preclinical AD and 123 controls with eight to 10 years of follow-up from the China Cognition and Aging Study. Plasma Aβ42, p-tau181 and NfL were significantly correlated with cerebrospinal fluid counterparts and significantly altered in participants with preclinical AD. Combining plasma Aβ42, p-tau181 and NfL successfully discriminated preclinical AD from controls. These findings were validated in a replication cohort including 51 familial AD mutation carriers and 52 non-carriers from the Chinese Familial Alzheimer’s Disease Network. Here, the authors show that plasma


Aβ42, p-tau181 and NfL may be useful for predicting AD eight years before clinical onset in Chinese populations.


Biomarkers in Alzheimer’s disease: role in early and differential diagnosis and recognition of atypical variants Dubois B, von Arnim CAF, Burnie N, Bozeat S, Cummings J. Alzheimers Res Ther. 2023 Oct 13; 15 (1): 175. doi: 10.1186/s13195-023-01314-6.


Development of in vivo biomarkers has shifted the diagnosis of Alzheimer’s disease (AD) from the later dementia stages of disease towards the earlier stages and has introduced the potential for pre-symptomatic diagnosis. The International Working Group


recommends that AD diagnosis is restricted in the clinical setting to people with specific AD phenotypes and supportive biomarker findings. In this review, the authors discuss the phenotypic presentation and use of biomarkers for the early diagnosis of typical and atypical AD and describe how this can support clinical decision- making, benefit patient communication, and improve the patient journey. Early diagnosis is essential to optimise the benefits of available and emerging treatments. As atypical presentations of AD often mimic other dementias, differential diagnosis can be challenging and can be facilitated using AD biomarkers. However, AD biomarkers alone are not sufficient to confidently diagnose AD or predict disease progression and should be supplementary to clinical assessment to help inform the diagnosis of AD.


Use of AD biomarkers with


incorporation of atypical AD phenotypes into diagnostic criteria will allow earlier diagnosis of patients with atypical clinical presentations that otherwise would have been misdiagnosed and treated inappropriately. Early diagnosis is essential to guide informed discussion, appropriate care and support, and individualised treatment. It is hoped that disease-modifying treatments will impact the underlying AD pathology; thus, determining the patient’s AD phenotype will be a critical factor in guiding the therapeutic approach and the assessment of the effects of interventions.


Plasma-based diagnostic and screening platform using a combination of biosensing signals in Alzheimer’s disease Kim HJ, Kim H, Park D, Yoon DS, San Lee J, Hwang KS. Biosens Bioelectron. 2023 Jun 15; 230: 115246. doi: 10.1016/j. bios.2023.115246.


Using biosensor to screen for Alzheimer’s disease (AD) facilitates early detection of AD with high sensitivity and accuracy. This approach overcomes the limitations of conventional AD diagnostic methods, such as neuropsychological assessment and neuroimaging analysis. Here, the authors propose a simultaneous analysis of signal combinations generated by four crucial AD biomarkers (Amyloid beta 1-40 [Aβ40], Aβ42, total tau 441 [tTau441], and phosphorylated tau 181 [pTau181]) by inducing a dielectrophoretic (DEP) force on a fabricated interdigitated microelectrode (IME) sensor. By applying an optimal DEP force, the biosensor selectively concentrates and filters the


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plasma-based AD biomarkers, exhibiting high sensitivity (limit of detection <100 fM) and selectivity in the plasma-based AD biomarkers detection (P<0.0001). Consequently, it is demonstrated that a complex combined signal comprising four AD-specific biomarker signals (Aβ40- Aβ42+ tTau441- pTau181) can differentiate between patients with AD and healthy subjects with high accuracy (78.85%) and precision (80.95%) (P<0.0001).


Biomarker disclosure protocols in prodromal Alzheimer’s disease clinical trials


Rahman-Filipiak A, Bolton C, Grill JD et al.; Advisory Group on Risk Evidence Education in Dementia (AGREED). Alzheimers Dement. 2023 Sep; 19 (9): 4270–5. doi: 10.1002/alz.13380.


The development of biomarkers for Alzheimer’s disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker ‘screening’ criteria should be met with a parallel implementation of standardised methods to disclose biomarker testing results to research participants; however, the extent to which protocolised disclosure occurs in trials is unknown. Here, the authors reviewed the


literature to identify prodromal AD trials published in the past 10 years. From these, they quantified the frequency of biomarker disclosure reporting and the depth of descriptions provided. Of 30 published trials using positron- emission tomography or cerebrospinal fluid-based amyloid positivity as an eligibility criterion, only one mentioned disclosure, with no details on methods. Possible reasons for and implications of this information gap are discussed. Recommendations are provided for trialists considering biomarker screening as part of intervention trials focused on prodromal AD. Few prodromal AD trial papers discuss biomarker disclosure. Disclosure has implications for participants, family members, and trial success. Disclosure must be consistently integrated and reported in prodromal AD trials. Best practice guidelines and training resources for disclosure are needed.


Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer’s Disease Rani S, Dhar SB, Khajuria A et al. Cell Mol Neurobiol. 2023 Aug; 43 (6): 2491–523. doi: 10.1007/s10571-023-01330-y.


The development of early non-invasive 53


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