Blood-based biomarkers may aid earlier diagnosis of Alzheimer’s disease

Blood-based biomarkers (BBBs) may potentially aid earlier detection of Alzheimer’s disease (AD) following a recent revision of diagnostic criteria supporting core biomarker–based diagnosis. Initial local experience with lecanemab, a disease-modifying therapy (DMT) for patients with mild cognitive impairment or mild dementia due to AD, was shared at Advances in Medicine (AIM) 2025.

 

Revised diagnostic and staging criteria

“The Alzheimer’s Association’s 2024 revised criteria for diagnosis and staging of AD represents a revolutionary change,” said Dr Felix Chan, Specialist in Geriatric Medicine in Hong Kong, at AIM 2025.

 

An abnormal core 1 biomarker (ie, amyloid-β 42 [Aβ42], or phosphorylated tau 217 [p-tau217], p-tau181 or p-tau231) result is now sufficient for establishing AD diagnosis and informing clinical decision-making throughout the disease continuum, as AD is defined as a biological process that begins with the appearance of AD neuropathologic change while individuals are asymptomatic. [Alzheimer’s Dement 2024;20:5143-5169]

 

Blood-based biomarkers may revolutionize AD diagnosis

New BBBs may revolutionize dementia work-up and facilitate earlier AD diagnosis, given the long waiting time for MRI or CT in Hong Kong’s public hospitals, where confirmatory amyloid PET is not routinely available.

 

One promising BBB is p-tau217, which is strongly associated with AD pathology. The percentage of plasma p-tau217 (ie, ratio of plasma p-tau217 to non–p-tau217) showed comparable diagnostic accuracy (90 percent) vs clinically approved cerebrospinal fluid biomarkers (ie, p-tau:Aβ42 ratio [91 percent] and Aβ42:Aβ40 ratio [87 percent]) in individuals with cognitive impairment assessed with Aβ PET in secondary care. [Nat Med 2024;30:1085-1095]

 

A recent study (n=1,213) conducted in primary and secondary care settings showed high diagnostic accuracy of 90 percent with percentage of p-tau217 alone for identifying AD among individuals with cognitive symptoms. Diagnostic accuracy was also 90 percent when percentage of p-tau217 was combined with plasma Aβ42:Aβ40 ratio (ie, amyloid probability score 2 [APS2]). [JAMA 2024;332:1245-1257]

 

Among primary care physicians, APS2 showed a diagnostic accuracy of 91 percent for identifying clinical AD, compared with 61 percent with clinical examination, cognitive testing and CT. Among dementia specialists, the diagnostic accuracy was 91 vs 73 percent.

 

“This may be the potential way forward for early detection of AD due to the noninvasiveness and much lower cost of blood testing,” suggested Chan. “Reliable BBBs may help guide the choice of DMT.”

 

HK experience with lecanemab

Among the two US FDA–approved DMTs for early AD, lecanemab is the first and currently the only agent available in Hong Kong. “We have nearly 1 year of clinical experience with lecanemab. As of May 2025, 11 patients had been treated in Hong Kong West. Most patients continued treatment. Two patients discontinued treatment due to amyloid-related imaging abnormalities [ARIA] [ARIA-haemorrhage, n=1; ARIA-oedema, n=1], and one patient discontinued treatment by his own decision,” reported Chan.

 

In this cohort (age, 65–84 years; baseline Montreal Cognitive Assessment score, 10–30), six patients had received ≥10 lecanemab infusions as of May 2025. “The patient treated for the longest duration had received 19 infusions. Her MRI scans had been clear of microbleeds,” said Chan.

 

While more data are being collected from this Hong Kong cohort, lecanemab’s pivotal phase III trial showed significantly less decline in cognitive and functional endpoints as well as significant reduction in amyloid burden vs placebo at 18 months. [N Engl J Med 2023;388:9-21] Three-year data demonstrated benefit with early start of treatment, especially in patients with low baseline amyloid burden. [van Dyck CH, AAIC, 2024] ARIA and infusion-related reactions were less common in Asians vs the trial’s overall population. [J Prev Alzheimers Dis 2025;12:100160]