A study published in Archives of Neurology demonstrated that the connection between two cerebrospinal fluid proteins that are linked to Alzheimer’s disease in clinically and cognitively normal older patients shows that amyloid-β (Aβ)-associated clinical decline was linked to the presence of higher phospho-tau (p-tau).

According to the researchers, as therapeutic interventions to prevent dementia are developed, it is vital to identify older individuals destined to developed Alzheimer disease (AD).

Rahul S. Desikan, M.D., Ph.D., of the University of California-San Diego School of Medicine, and his team assessed 107 healthy people from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The the team used the global Clinical Dementia Rating (CDR) scale and the Alzheimer Disease Assessment Scale-cognitive subscale in order to analyze the relationship of cerebrospinal fluid (CSF) levels of phospho-tau 181 (p-tau 181p ) and CSF Aβ 1-42 with clinical decline.

The researchers found that the relationship between decreased CSF Aβ 1-42 and change in those assessment measures in individuals with increased CSF p-tau 181p was significant.

The researchers said:

“These findings provide important insights into the preclinical stage of AD. Consistent with prior studies, our results indicate that in clinically normal older individuals, Aβ deposition by itself is not associated with clinical decline; the presence of p-tau represents a critical link between Aβ deposition and accelerated clinical decline. Furthermore, our findings point to p-tau as an important marker of AD-associated degeneration.”

Even though findings from this study suggest that CSF Aβ 1-42 in combination with CSF p-tau 181p “may better predict clinical decline” than CSF Aβ 1-42, in combination with CSF t-tau, the researchers highlight that earlier studies have demonstrated that CSF Aβ 1-42, combined with CSF p-tau and t-tau, are “equally predictive of decline.”

According to the researchers, both the CSF p-tau 181p and CSF Aβ 1-42 status of participants should be considered in early intervention trials. Furthermore, results from the study underline the need to develop treatments that specifically target tau.

The researchers conclude:

“It is feasible that although Aβ initiates the degenerative cascade, elevated levels of tau may represent a second phase of the AD pathologic process where neurodegenerative changes occur largely independent of Aβ.”

In an associated report, David M. Holtzman, M.D., of Washington University, St. Louis said:

“If both academic groups and the pharmaceutical industry are going to move toward prevention trials to delay the onset of cognitive impairment and dementia, biomarkers will need to be used to select people who are clinically normal but at high risk for near-term cognitive decline.

Without such an approach, trial size will be enormous and cost prohibitive, and individuals may be subjected to treatments that have the potential for toxicity with no clear benefit.

Results from this new study, as well as previous studies with similar findings, strongly suggest that in otherwise health individuals aged 55 to 85 years, use of these CSF biomarkers may allow for selection of approximately 20 percent of such a population that meet the criteria for the presence of amyloid deposition and neurodegeneration to select for a secondary prevention trial that could be completed with a clinical and cognitive readout during a 3-year period.”

Holtzman concludes:

“The ultimate goal in treating any disease is to delay or prevent its occurrence. With the looming epidemic of AD, we are now at the point where we can and need to design rational trials to delay or prevent dementia.”

Written By Grace Rattue