Blood Biomarkers Linked to Brain Atrophy as New Tools Advance Neurodegeneration Detection

Recent studies have linked blood-based biomarkers to specific patterns of brain atrophy and cognitive decline in Alzheimer's disease, while other research initiatives are advancing retinal imaging, speech analysis, and DNA aptamers as tools for detecting and monitoring neurodegeneration.

In a study published in Neurology, investigators from Vrije Universiteit Amsterdam evaluated longitudinal associations between blood-based biomarkers and brain atrophy in 167 participants with subjective cognitive decline. Participants underwent repeated blood sampling and MRI scans. Results showed that both baseline levels and longitudinal increases in GFAP were linked with greater atrophy across almost all AD-signature brain regions, baseline plasma pTau217 was linked with atrophy across a number of medial temporal regions, and longitudinal pTau217 increases were associated with atrophy primarily in temporal regions. Using exploratory analysis, the investigators estimated that changes in pTau217 preceded hippocampal atrophy by 19.8 years (range, 10.7-43.7 years). Overall, these findings indicate that different blood-based biomarkers are associated with distinct areas of brain atrophy, supporting the use of both pTau217 and GFAP for early identification of disease and monitoring of disease progression in patients with AD.

Alzheimer disease neuropathology is associated with worse cognitive performance, according to a study published in the May 30 issue of The Lancet. Researchers from the University of California San Francisco examined participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with available plasma biomarkers at year 35. Of the 2,248 participants who completed the year 35 visit, 1,500 were randomly selected for plasma biomarker measurement; the final cohort included 1,350 participants (mean age, 61 years). Alzheimer disease neuropathology positivity was seen in 6, 15, and 4 percent of participants based on p-tau217/Aβ42, Aβ42/40, and p-tau217, respectively, and was associated with worse performance on processing speed and executive function. Compared with negativity, positivity was associated with increased odds of accelerated decline on verbal memory (odds ratios, 4.31 and 2.44 for Aβ42/40 and p-tau217/Aβ42, respectively) and processing speed (odds ratios, 3.98 and 3.35 for p-tau217 and p-tau217/Aβ42, respectively). The senior author said in a statement that "these blood tests should be used with caution," but for some people who discover they have the biomarkers, testing could open a window to interventions that may postpone Alzheimer's onset.

In hereditary transthyretin (ATTRv) amyloidosis, serum neurofilament light chain (NfL) represents a promising non-invasive biomarker for assessment of early symptomatic disease and monitoring of disease progression, according to a study of patients with ATTRV30M amyloidosis and pre-symptomatic gene carriers. The study analysed serum samples from 34 ATTRV30M patients, 17 pre-symptomatic ATTRV30M carriers, and 35 controls. Serum NfL levels were significantly elevated in ATTRV30M patients compared with controls (threefold, p = 0.0005) and were 1.6-fold higher than in pre-symptomatic carriers; no significant differences were observed between pre-symptomatic carriers and controls. NfL concentrations were higher in patients with polyneuropathy disability score > I compared with PND I (p = 0.0007). Serum GFAP and peripherin levels did not differ significantly among the study groups.

Alpha-synuclein blood biomarkers are an important area of investigation in Parkinson's disease and synucleinopathy studies. The misfolding and aggregation of α-synuclein form pathological inclusions known as Lewy bodies and Lewy neurites, hallmarks of synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Both total α-synuclein and pS129-α-synuclein are attractive biomarkers; within Lewy bodies, over 90% of α-synuclein is phosphorylated at serine 129. Blood-based biomarkers may provide a less intrusive and more scalable pathway for recurrent sampling, longitudinal investigations, and larger translational research.

An international team with Universitat Oberta de Catalunya participation developed a general index for brain asymmetry that analyses uneven deterioration in different brain regions. The researchers found that the higher the index value, the more asymmetry in the brain, which correlates with greater neurodegeneration and more symptoms. The study used a cohort of 60 participants from Hospital Clínic in Barcelona and 564 individuals from the DIAN project, and found the index could distinguish between people with Alzheimer's disease and healthy people, determine disease progress, and assess effectiveness of new drugs. It was also able to identify carriers of the APOE4 genotype who have symptoms and carriers of the genetic mutation associated with the condition who do not have symptoms. The researchers are working to replicate the results in people with sporadic Alzheimer's disease.

At the Duke Eye Center, the Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) initiative, launched in 2017, combines high-resolution retinal imaging, longitudinal clinical data, and machine learning approaches to study neurodegenerative disease. iMIND is investigating whether multimodal retinal imaging, including optical coherence tomography and optical coherence tomography angiography, can detect disease-specific signatures across Alzheimer disease, mild cognitive impairment, and Parkinson disease. The iMIND research director said the microvascular circulation is directly visible in only one place in the body — the neurosensory retina — and that the retina allows study of both microvascular and neural information noninvasively. In cross-sectional work recently submitted for peer review, the team found that patients with dementia with Lewy bodies tend to have more microvascular loss in the retina than those with Alzheimer disease, in particular more pronounced central macular microvascular impairment.

SynaptixBio has highlighted the potential of speech analysis as a non-invasive way to track disease progression in neurodegenerative conditions as a new study gets underway in patients with H-ABC. The research, led by Murdoch Children's Research Institute in partnership with speech analytics company Redenlab and facilitated by SynaptixBio, will assess whether changes in communication can act as an indicator of brain health. The study is open to patients aged from six months to adulthood worldwide and is designed to capture speech, sign language, gestures, and assistive devices. SynaptixBio's chief medical officer said speech parameters may be powerful tools for detecting early treatment effects prior to established clinical rating scales. The company plans to include speech-based measures as exploratory endpoints in future clinical trials. The study will be conducted entirely online and is available in multiple languages. Redenlab said advances in digital analysis, including artificial intelligence, could enable more objective assessment of speech patterns such as clarity, pause length and vocabulary use.

Researchers from Japan have developed the world's first aptamer — tiny, single-stranded synthetic DNA molecules — that can bind NfL with high affinity and specificity. The aptamers were generated through seven rounds of SELEX selection, yielding 86 unique aptamer candidates, of which 30 sequences successfully recognized full-length NfL. Two aptamers, named MN711 and MN734, bound NfL with dissociation constants of 11 nM and 8.1 nM, respectively, and were highly specific, binding only to NfL over other AD-related biomarkers like amyloid β and phosphorylated tau. The aptamers recognized a specific region of the NfL protein containing amino acid residues 281–338, and binding was maintained in human plasma. DNA aptamers combine high affinity and specificity with practical advantages: they are chemically synthesized, can be produced with minimal batch-to-batch variation, and can be readily modified for use in biosensors. The work was made available online on December 16, 2025, and published in Volume 796 of Biochemical and Biophysical Research Communications on January 18, 2026.

An Indian study has identified a potential connection between neurodegenerative biomarkers and sarcopenia, a condition characterized by the progressive loss of muscle mass and strength in aging populations. Researchers found that elevated levels of NfL and GFAP may be linked to the development of sarcopenia in elderly individuals, with higher concentrations consistently associated with more severe cases of sarcopenia. The findings suggest a possible biochemical relationship between neurological health and muscle deterioration, and could pave the way for earlier detection methods or targeted interventions.