Jia J, Ning Y, Chen M, Wang S, Yang H, Li F, Ding J, Li Y, Zhao B, Lyu J, Yang S, Yan X, Wang Y, Qin W, Wang Q, Li Y, Zhang J, Liang F, Liao Z, Wang S. Biomarker Changes during 20 Years Preceding Alzheimer's Disease. N Engl J Med. 2024 Feb 22;390(8):712-722. PubMed.
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San Francisco Veterans Affairs Medical Center
These two papers describing the timeline of the trajectory from amyloid positivity to symptom onset are extremely important, with very practical implications for clinical trials and patient care. What is so remarkable is how similar the results are in these two studies: a U.S., largely white population population and a Chinese population.
We can expect that these results will lead to additional studies using plasma markers. In the long term, as more data becomes available, we can be hopeful that a “precision medicine” approach may be possible to inform individual patients about their relative risk and possible timeline for development of future symptoms.
View all comments by Michael WeinerHospital de Sant Pau
This impressive study characterizes the longitudinal biomarker changes in sporadic AD. The pattern of changes in other forms of AD, such as autosomal-dominant AD (Bateman et al., 2012) or Down Syndrome AD (Fortea et al., 2020) have previously been reported. However, the course of sporadic AD has been less characterized. One of the challenges is that sporadic AD is highly heterogeneous in term of pathophysiology, with different underlying biological subtypes that lead to different progression rates (Tijms et al., 2020).
In this study, Jia et al. confirm the long preclinical phase of the disease of sporadic AD; however, the exclusion of patients with positive family history makes it difficult to generalize the results to the bulk of patients seen in memory units or to patients enrolled in clinical trials. In any case, the long follow-up and the large sample size help to shed light on the complex biology of the common form of AD.
References:
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Tijms BM, Gobom J, Reus L, Jansen I, Hong S, Dobricic V, Kilpert F, Ten Kate M, Barkhof F, Tsolaki M, Verhey FR, Popp J, Martinez-Lage P, Vandenberghe R, Lleó A, Molinuevo JL, Engelborghs S, Bertram L, Lovestone S, Streffer J, Vos S, Bos I, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Blennow K, Scheltens P, Teunissen CE, Zetterberg H, Visser PJ. Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics. Brain. 2020 Dec 1;143(12):3776-3792. PubMed.
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