First ever large-scale human study validates multiple biomarkers for Alzheimer’s disease.
Through studying brain scans and cerebrospinal fluid of healthy adults researchers at Washington University have shown that changes in key biomarkers of Alzheimer’s disease during midlife can help identify those who will develop dementia years later. The study is published in JAMA Neurology.
The current study focused on data gathered over 10 years and involved 169 cognitively normal research participants ages 45 to 75 when they entered the study. Each participant received a complete clinical, cognitive imaging and cerebrospinal fluid biomarker analysis every three years, with a minimum of two evaluations. At the participants’ initial assessments the researchers divided them into three age groups; early-middle age (45-54); mid-middle age (55- 64); and late-middle age (65-74).
Among the biomarkers evaluated in the current study were, amyloid beta 42, a protein that is the principal ingredient of Alzheimer’s plaques; Tau, a structural component of brain cells that increases in the cerebrospinal fluid as Alzheimer’s disease damages brain cells; YKL-40, a newly recognized protein that is indicative of inflammation and is produced by brain cells; and the presence of amyloid plaques in the brain, as seen via amyloid PET scans.
The data findings show that drops in amyloid beta 42 levels in the cerebrospinal fluid among cognitively normal participants ages 45-54 are linked to the appearance of plaques in brain scans years later. The results also showed that tau and other biomarkers of brain-cell injury increase sharply in some individuals as they reach their mid-50s to mid-70s, and YKL-40 rises throughout the age groups focused on in the study.
Previous research has shown that all of these biomarkers may be affected by Alzheimer’s disease, however, the team state that to their knowledge this is the first large data set to show that the biomarkers change over time in middle-aged individuals.
The current study found that all of these changes were more pronounced in participants who carried a form of a gene that significantly increases the risk of Alzheimer’s disease. The gene is known as APOE, with earlier studies showing that people with two copies of a particular version of this gene have up to 10 times the risk of developing Alzheimer’s as those with other versions of the gene.
The data came from the ongoing Adult-Children Study at the university’s Charles F. and Joanne Knight Alzheimer’s Disease Research Center. The team have been following participants with and without a family history of the disease, with the aim of identifying Alzheimer’s biomarkers most closely associated with the development of full-blown disease years later.
The team stress that although it’s too early to use these biomarkers to definitively predict whether individual patients will develop Alzheimer’s disease, they are working toward that goal. They go on to add that one day they hope to use such measures to identify and treat people years before memory loss and other cognitive problems become apparent. The researchers conclude that Alzheimer’s is a long-term process, and that means people must be observed for a long time to catch glimpses of it in action.