In 1906, Alois Alzheimer reported “a peculiar severe disease process of the cerebral cortex” (1). This dementia, involving amyloid-plaques and tau neurofibrillary tangles, would later be called Alzheimer’s disease (AD). Decades later, Braak and Braak described neuropathological staging of AD based on neuroanatomic immunostaining of tau correlating well with cognitive decline. Amyloid plaques, however, were of limited value for this purpose partly because amyloid-beta (Aβ) pathology is widespread once in symptomatic AD.
Neuropathological evidence of tau tangles and Aβ plaques remain the gold standard method for confirmatory diagnosis of AD. However, AD is often clinically diagnosed based on symptoms reflecting AD-type dementia that nonetheless overlap with other dementias, contributing to approximately one-in-three misdiagnosis rate compared with neuropathology. Biomarkers that can report on the disease may help improve the situation.
In 1995, Blennow and colleagues reported that tau phosphorylated at threonine-181 (p-tau) is distinctively released into cerebrospinal fluid (CSF) with increasing severity of AD; however, this biomarker was unchanged in other neurodegenerative diseases (2). Conversely, non-phosphorylated tau (“total-tau”) became abnormal in AD and several other neurological diseases(2). Subsequently, these assays were developed into different commercial tests on different technology platforms. Independent validation of the initial findings have resulted in the inclusion of p-tau and total-tau analyses in clinic and research guidelines for AD.
In living individuals, AD diagnosis currently relies on two main strategies: (i) CSF changes in p-tau, total tau and Aβ, and (ii) brain imaging of tau tangles and Aβ plaques by positron emission tomography (PET). CSF p-tau and tau PET are highly specific for AD pathophysiology. However, their utility is limited by invasiveness, complexity, and poor accessibility. Therefore a simple blood test that can detect diseaserelated changes will be highly advantageous.
Det här är ett utplock av en intressant artikel från KBN – Nr. 4 – vol. 32 – 2020.