Alzheimer’s blood tests are advancing diagnosis. What can they really tell us?

Changes in the brain linked to Alzheimer’s disease can begin years before memory and other cognitive symptoms appear. Blood-based biomarkers offer a less invasive way to detect some of these biological changes. These include phosphorylated tau (p-tau), such as p-tau217 and p-tau181, and amyloid-beta measures such as the Aβ42/Aβ40 ratio. However, these tests do not directly measure memory loss, brain-cell loss or the severity of cognitive impairment.What do these tests detect?Tau is a protein found in nerve cells. In Alzheimer’s disease, abnormal tau is linked to the formation of neurofibrillary tangles. The build-up of amyloid-beta is another biological change associated with the disease.Blood tests do not directly detect plaques or tangles in the brain. They measure proteins or changes in proteins in the blood that can reflect processes taking place in the brain.“P-tau217 has shown the strongest diagnostic performance among the available blood biomarkers for detecting Alzheimer-related pathology, especially when combined with simultaneous measurement of the beta-amyloid proteins,” said Srikanth Srinivasan, senior consultant, neurology and specialist in neuropsychiatry, Apollo Hospitals, Greams Road, Chennai.“These tests are emerging tools for detecting biological changes associated with Alzheimer’s,” said Prabash Prabhakaran, director and senior consultant, neurology, SIMS Hospital, Chennai.A positive result from a well-validated test makes Alzheimer’s-related pathology more likely. But it does not mean that a person has Alzheimer’s dementia. “Alzheimer’s disease pathology and clinical dementia are not the same thing,” Dr. Srinivasan said. A person can have Alzheimer’s-related changes in the brain without significant problems with memory or thinking.What does a positive result mean?A blood biomarker gives information about disease biology, not a timetable for dementia.A positive result cannot tell when symptoms will begin, how quickly cognitive decline may occur or whether an asymptomatic person will necessarily develop dementia. Risk is influenced by factors such as age, genetics, vascular health, cognitive reserve and other brain pathologies.“The test must not be interpreted as a countdown to dementia,” Dr. Prabhakaran said.It also cannot establish that Alzheimer’s is responsible for all of a person’s cognitive symptoms, as mixed brain pathologies are common in older people.A negative result lowers the likelihood of Alzheimer’s-related pathology, but does not rule out every other cause of cognitive impairment.Where does it fit in diagnosis?Blood biomarkers are currently used mainly in people with objectively documented cognitive impairment who are being evaluated to determine its cause.The 2025 Alzheimer’s Association clinical practice guideline recommends blood-based biomarker testing in specialised care settings for people with objective cognitive impairment when Alzheimer’s disease is suspected. It does not recommend testing cognitively unimpaired people.The blood test follows, rather than replaces, clinical assessment. This includes a detailed history from the patient and, where possible, a caregiver; cognitive testing; neurological examination; and a review of medications, sleep, mood and other medical conditions.Doctors may also look for potentially reversible causes such as thyroid disorders, vitamin B12 deficiency, metabolic abnormalities and depression. MRI or CT may be used to assess structural changes and other possible causes.“Blood-based biomarkers should be interpreted along with the person’s symptoms, cognitive assessment and medical history,” Dr. Srinivasan said.CSF testing or amyloid PET may still be needed when blood-test results are borderline, do not match the clinical picture or when greater diagnostic certainty is required.Not all blood tests are the same“Alzheimer’s blood test” can refer to different biomarkers, assays and testing platforms.P-tau217, p-tau181, p-tau231 and amyloid-beta ratios are not interchangeable. Different assays and cut-offs can have different levels of accuracy.The guideline recommends at least 90% sensitivity and 75% specificity for blood tests used for triage. For tests intended to confirm Alzheimer’s pathology, it recommends at least 90% for both sensitivity and specificity. These are performance thresholds for specific clinical uses and do not mean every commercial test has the same accuracy.People considering testing should ask which biomarker is being measured, which assay is being used, which population it has been validated in and what cut-offs the laboratory uses, Dr. Srinivasan said.“The test should be ordered when the result is likely to answer a specific clinical question,” he said.What about people without symptoms?Using blood tests to identify Alzheimer’s-related changes before symptoms appear is an active area of research. But finding preclinical pathology does not by itself show that routine testing of healthy people is useful.Sunil K. Narayan, dean, medical research, and head of the department of neurology, SRM Medical College Hospital and Research Centre, said occasional forgetfulness alone should not be assumed to indicate dementia. Persistent changes that affect everyday functioning warrant clinical evaluation.The scenario in IndiaBlood-based Alzheimer’s biomarker testing is becoming available through some private laboratories and specialised centres in India, Dr. Srinivasan said, but its clinical use and standardisation are still evolving.A 2026 analysis from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), involving 4,635 adults aged 60 and above, found that higher NfL and GFAP levels were associated with poorer cognition after adjustment for several factors. The association with p-tau181 was not robust after adjustment. The authors called for longitudinal validation.Experts said wider clinical use in India would require multi-centre validation in Indian populations, assay-specific cut-offs, standardised sample handling, external quality assessment, regulatory clarity, affordable confirmatory testing and specialist counselling. They also highlighted the need for indigenous research and development of biomarker technologies.