Amyloid and Tau Biomarkers of Alzheimer Disease Found in Individuals with Other Dementias
Biomarkers in a pattern characteristic of Alzheimer pathology were identified in unspecified dementia, Parkinson dementia, and frontotemporal dementia.
Alzheimer disease (AD) biomarkers appear more frequently in other forms of dementia than previously recognized, according to a large cross-sectional study conducted in Sweden. Among nearly 14,000 adults with various dementia diagnoses, cerebrospinal fluid (CSF) markers traditionally associated with Alzheimer — amyloid-beta 1-42 (Aβ1-42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) — were prevalent in people with AD but also in those with unspecified dementia, Parkinson disease dementia, and frontotemporal dementia.
The findings, published in JAMA Neurology, suggest that Alzheimer’s-like pathology may play a broader role across multiple dementia types and could have implications for expanding disease-modifying treatments, according to first author Tobias Borgh Skillbäck, MD, PhD, of Sahlgrenska University Hospital in Molndal, Sweden, and co-authors.
For the cross-sectional study Skillbäck et al merged archived CSF measurements from clinical practice at the Sahlgrenska University Hospital with data from the SveDem national dementia registry, spanning 12 years (October 2010 through August 2022).
The researchers found that 68% of individuals diagnosed with early-onset Alzheimer’s disease exhibited the classic AD biomarker profile, characterized by abnormal levels of Aβ1-42, t-tau, and p-tau181, while 65% of those with late-onset Alzheimer’s and 52% with mixed AD and vascular dementia also showed the characteristic pattern. Notably, among those in the dementia not otherwise specified group, ie, without a formal AD diagnosis, 25% had a clear AD-like biomarker profile, while Parkinson disease dementia and the frontotemporal dementia groups had the smaller shares (9% and 8%, respectively), according to the findings.
As expected, people with AD displayed low CSF Aβ1-42 levels alongside elevated t-tau and p-tau181 concentrations. However, the presence of amyloid and tau pathology extended well beyond typical AD diagnoses.
“We identified large shares of patients who were CSF amyloid- and tau-positive in clinically diagnosed groups with non-Alzheimer’s dementia, including Parkinson’s disease dementia, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and other dementias,” Skillbäck and colleagues noted. This was observed even though the majority of patients (85%) received their diagnoses in specialist care settings and after CSF testing (88%).
The investigators also found that cognitive function, assessed using the Mini-Mental State Examination (MMSE), was linked to these biomarkers across several dementia types. MMSE scores were associated with Aβ1-42 in late-onset AD, vascular dementia, frontotemporal dementia, and unspecified dementia. Additionally, t-tau correlated with MMSE scores in late- and early-onset AD and unspecified dementia, while p-tau181 was tied to cognitive function in early-onset AD, they reported.
The researchers acknowledged that using clinical CSF data could introduce circular reasoning, as most Alzheimer’s-diagnosed patients already had Alzheimer’s-like biomarker profiles. “The obvious risk of circular reasoning precludes further conclusions from being drawn from this finding,” Skillbäck and colleagues wrote. “However, this would not negatively influence the conclusions of this study, as a main point is that amyloid pathology is common in other dementias as well.”
Median age of study the 13,882 participants was 74 years and 53% were women. had a dementia diagnosis and a full set of CSF biomarker measurements taken within 3 years of their diagnosis, with a median gap of 9 weeks between diagnosis and sampling. Pathological biomarker levels were defined based on harmonized reference values—CSF β1-42 levels below the reference threshold and t-tau and p-tau181 levels above their respective reference values.
The authors acknowledged several limitations to the study including reliance reliance on MMSE scores as a proxy for cognitive function. Nonetheless, they noted that their findings align with previous autopsy studies2 identifying amyloid plaques and tau tangles in dementia types not traditionally associated with Alzheimer’s, such as frontotemporal dementia, reinforcing the need to consider overlapping pathological mechanisms across neurodegenerative diseases.
