Two Proteins Needed to Turn on Dementia

Cognitive decline in older individuals who have amyloid-beta deposition only occurs when they also have high levels of a specific tau protein, a longitudinal study found.

Having amyloid-beta peptides 1-42 present in the cerebrospinal fluid was associated with changes on the clinical dementia rating scale exclusively among patients who also had phosphorylated (p) tau181p present at elevated levels (β1=0.06, P=0.01), according to Rahul S. Desikan, MD, PhD, of the University of California San Diego, and colleagues.

In contrast, individuals who were positive for amyloid-beta1-42 but negative for p-tau181p showed no evidence of decline (β1= -0.02, P=0.35), the researchers reported online in the Archives of Neurology.

"Our results indicate that in clinically normal older individuals, amyloid-beta deposition by itself is not associated with clinical decline; the presence of p-tau represents a critical link between amyloid-beta deposition and accelerated clinical decline," they stated.

Previous research has demonstrated a clear association between amyloid-beta deposition and the later development of Alzheimer's disease, even 10 to 15 years before signs of dementia begin to appear.

However, recent animal studies have suggested that the protein tau also contributes to the injury to neurons and synapses characteristic of Alzheimer's disease, and that low levels of tau appear to be protective.

Recent studies suggest that the use of cerebrospinal fluid and amyloid imaging can detect the presence of amyloid deposition beginning as early as 10 to 15 years prior to the onset of any clinically detectable cognitive decline from Alzheimer's disease.

In this study, researchers found that cognitive decline in older individuals who have amyloid-beta deposition only occurs when they also have high levels of a specific tau protein.

To see if clinical decline correlated with the two proteins, Desikan and colleagues obtained cerebrospinal fluid samples from 107 participants in the Alzheimer's Disease Neuroimaging Initiative who were cognitively normal at baseline, following them for 3 years.

Cognitive decline refers to diminished and impaired cognitive functioning, which is a person's capacity to think, make decisions, use language and learn and remember information. Dementia refers to a group of symptoms caused by illnesses and injuries of the brain. Types There are various types of dementia, including Alzheimer's disease, vascular dementia, Lewy body dementia and frontotemporal dementia. Cognitive impairment is more noticeable and pronounced than a normal level of forgetfulness, according to the website of the Mayo Clinic.

Average age was 76, and more than two-thirds were men.

At follow-up, cognition was assessed on the global clinical dementia rating scale; the sum of boxes test, which summarizes function in various domains such as memory and problem-solving; and the Alzheimer Disease Assessment Scale-cognitive subscale.