Skip to main content
main-content
Top

24-04-2012 | Psychology | Article

tau protein provides missing link between amyloid plaques and clinical decline

Abstract

Free abstract

MedWire News: Amyloid-β (Aβ) plaque deposition in brain tissue is related to clinical decline in cognitively normal older adults only if they also have high levels of hyperphosphorylated tau protein (p-tau), US study data show.

These findings "provide important insights into the preclinical stage of Alzheimer's Disease (AD)," and indicate that "p-tau represents a critical link between Aβ deposition and accelerated clinical decline," write Rahuk Desikan (University of California-San Diego) and colleagues in the Archives of Neurology.

The researchers say that the identification of clinically normal older individuals destined to develop AD is of increasing clinical importance as therapeutic interventions for the prevention of dementia are developed.

Prior experimental evidence indicates that Aβ deposition triggers the neurodegenerative process underlying AD. However, amyloid plaques correlate poorly with memory decline and immunotherapy-induced plaque removal may not prevent progressive neurodegeneration, suggesting that other entities may be required for AD-related degeneration.

One such entity may be p-tau, a marker of neurodegeneration, and in the present study, Desikan and team investigated its relationship with Aβ and clinical decline over time among 107 cognitively normal (Clinical Dementia Rating [CDR] of 0 at baseline examination) men and women aged 70 years and older.

During a mean 3-year follow-up period, the researchers assessed clinical decline using longitudinal change in global CDR, CDR-Sum of Boxes (SB), and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). The also measured cerebrospinal fluid (CSF) levels of p-tau181p and Aβ1-42.

The team observed a significant relationship between positive CSF Aβ1-42 status (<192 pg/mL) and longitudinal change in global CDR, CDR-SB, and ADAS-cog, but only among individuals with elevated CSF p-tau181p (>23 pg/mL).

In the absence of CSF p-tau181p, there was no significant association between CSF Aβ1-42 status and change in global CDR, CDR-SB, and ADAS-cog.

"Our findings point to p-tau as an important marker of AD-associated degeneration," Desikan et al remark.

They say that in light of these data, early intervention trials should consider both the CSF p-tau181p and CSF Aβ1-42 status of participants because older individuals with increased CSF p-tau181p and decreased CSF Aβ1-42 levels are likely to have a different rate of clinical progression to individuals with normal CSF p-tau181p and decreased CSF Aβ1-42 levels.

They add: "These findings also illustrate the need for developing novel therapeutic approaches that specifically target tau.

"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.

"As such, targeting downstream events, such as tau phosphorylation and aggregation, in older individuals with both decreased CSF Aβ1-42 and increased CSF p-tau181p levels may be an additionally beneficial treatment strategy," the researchers conclude.

By Laura Cowen

Related topics