New research shows for the first time that PET scans can track the progressive stages of Alzheimer’s disease in cognitively normal adults, a key advance in the early diagnosis and staging of the neurodegenerative disorder.

In the process, the scientists also obtained important clues about two Alzheimer’s-linked proteins – tau and beta-amyloid – and how they relate to each other.

The findings, published in the journal Neuron, come from positron emission tomography (PET) of 53 adults. Five were young adults aged 20-26, 33 were cognitively healthy adults aged 64-90 and 15 were patients aged 53-77 who had been diagnosed with probable Alzheimer’s dementia.

PET scans are used to detect early signs of disease by looking at cellular-level changes in organs and tissue. The results of the scans in this study paralleled Braak neuropathological stages, which range from one to six, describing the degree of tau protein accumulation in the brain.

The findings also shed light on the nature of tau and amyloid protein deposits in the aging brain. For many years, the accumulation of beta amyloid plaques was considered the primary culprit in Alzheimer’s disease. Over the past decade, however, tau, a microtubule protein important in maintaining the structure of neurons, has emerged as a major player. When the tau protein gets tangled and twisted, its ability to support synaptic connections becomes impaired.

While a number of symptoms exist that signal Alzheimer’s disease, a definitive diagnosis has been possible only through an examination of the brain after the patient has died. The availability of amyloid imaging for the past decade has improved this situation, but how Alzheimer’s developed as a result of amyloid remains a mystery. Studies done in autopsies linked the development of symptoms to the deposition of the tau protein.

Through the PET scans, the researchers confirmed that with advancing age, tau protein accumulated in the medial temporal lobe — home to the hippocampus and the memory center of the brain.

The study revealed that higher levels of tau in the medial temporal lobe was associated with greater declines in episodic memory, the type of memory used to code new information. The researchers tested episodic memory by asking subjects to recall a list of words viewed 20 minutes earlier.

One question yet to be answered is why so many people have tau in their medial temporal lobe yet never go on to develop Alzheimer’s. Likewise, adults may have beta amyloid in their brains and yet be cognitively healthy.

While higher levels of tau in the medial temporal lobe was linked to more problems with episodic memory, it was when tau spread outside this region to other parts of the brain, such as the neocortex, that researchers saw more serious declines in global cognitive function. Significantly, they found that tau’s spread outside the medial temporal lobe was connected to the presence of amyloid plaques in the brain.

What the study does indicate is that tau imaging could become an important tool in helping to develop therapeutic approaches that target the correct protein — either amyloid or tau — depending on the disease stage.

Source: Sarah Yang, UC Berkeley

Links

UC Berkeley
"PET Imaging of Tau Deposition in the Aging Human Brain"