Longevity
Early-onset Alzheimer's shows faster, wider tau buildup than late-onset disease
By John Hyland, . Life and Health Today.
What the study found
People who develop Alzheimer's disease before age 65 accumulate tau protein faster, in greater quantities, and across a wider area of the brain than people whose symptoms begin after that age, according to imaging data published in the journal Science Translational Medicine.
Tau is a protein that, when it misfolds and clumps into tangles inside brain cells, is one of the two hallmarks of Alzheimer's disease. The other is amyloid-beta, a protein that forms plaques between cells. Researchers used tau PET imaging, a scanning technique that tracks tau tangles in living patients, to compare how the protein behaved in the two groups over time.
The study, led by Konstantinos Chiotis, MD, PhD, of the Karolinska Institutet in Stockholm, compared 390 early-onset patients with a mean age of 59 against 211 late-onset patients with a mean age of 78. All participants had confirmed amyloid pathology and mild cognitive impairment or mild dementia. A subset underwent follow-up scans over two to three years, making this the largest study to compare tau dynamics in both forms of the disease, according to MedPage Today.
"Younger patients had substantially more tau even after accounting for differences in clinical severity," Chiotis said in a statement reported by MedPage Today. "Their tau also accumulated faster over time. Delayed diagnosis alone does not explain this pattern."
How the two groups differed
At the start of the study, early-onset patients already showed higher amyloid PET binding and worse scores on standard cognitive tests, including the Mini-Mental State Examination and the Clinical Dementia Rating Sum of Boxes. Over the follow-up period, they accumulated tau tangles faster in every brain region examined.
The gap between the groups was larger for tau than for amyloid. Chiotis and co-authors wrote in Science Translational Medicine that the differences in tau burden between early- and late-onset patients were substantially larger than the differences in amyloid burden, consistent with findings from neuropathological studies conducted after death.
Tau buildup also correlated more strongly with amyloid accumulation and with broader cognitive decline in the younger group, suggesting the two pathologies may interact differently depending on when the disease begins.
Nicolai Franzmeier, PhD, of Ludwig Maximilians University in Munich, who was not involved in the study, told MedPage Today that the results "considerably strengthens previous evidence that linked younger age at symptom onset to more extensive tau pathology."
A different clinical picture
Early-onset Alzheimer's also presents differently at the bedside. Co-author Renaud La Joie, PhD, of the University of California San Francisco, noted in a statement that younger patients are more likely to experience symptoms unrelated to memory, at least initially. He described difficulties interpreting visual information despite normal eye exams, trouble judging distances, problems retrieving words, and challenges with executive functions such as attention and planning. Nearly one in five early-onset patients in this study had a non-amnestic presentation, meaning their primary symptoms were not memory-related, while 99.25 percent of late-onset patients presented with memory problems.
The early-onset group also had a higher proportion of women (55 percent versus 42 percent) and more participants already diagnosed with dementia at baseline (72 percent versus 36 percent).
What this does and does not establish
Early-onset Alzheimer's accounts for roughly 5 percent of all Alzheimer's cases, according to MedPage Today, though some research suggests young-onset forms of Alzheimer's and related dementias may be more common than previously recognized.
The researchers noted that why early-onset disease develops remains unclear. The study draws on two established cohorts: early-onset patients came from the Longitudinal Early-Onset Alzheimer's Disease Study, and late-onset patients from the Alzheimer's Disease Neuroimaging Initiative repository. Because the two groups came from different cohorts, differences in how participants were selected or followed could influence the comparison.
What the study establishes is that the biological trajectory of early-onset Alzheimer's is measurably different from the late-onset form, and that the difference is not simply a matter of being sicker at diagnosis. Whether that distinction should change how early-onset patients are monitored, enrolled in trials, or treated is a question the data point toward but do not answer.
Source: https://www.medpagetoday.com/neurology/alzheimersdisease/123876
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