In the afternoon of May 21st, Shenzhen Luohu Hospital Group, together with Prof. Wiltfang, Head of Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, successfully organized the Sino-German Video Conference on Alzheimer's Dementia to discuss the latest research on Alzheimer's Dementia. Zhu Feiqi, Director of Ward of Geriatric Cognitive Impairment, Shenzhen Luohu Hospital Group, hosted the conference and shared the experimental outcome on AD blood test of his team, and the medical staff of Ward of Geriatric Cognitive Impairment of Shenzhen Luohu Hospital Group participated in the conference.
The World Alzheimer's Dementia Report in 2018 showed that approximately one person with dementia is incurred every three seconds worldwide. Currently, there are at least 50 million people suffering from dementia worldwide, and it is expected to reach 152 million by 2050, of which about 60-70% are Alzheimer's Dementia (AD) patients. The global medical community is still at its wits' end with this disease and early intervention has become an important direction in the prevention and treatment of AD.
Blood-based dementia testing - an update
Since 2017, blood-based early and differential diagnosis is rapidly evolving to enable pre-clinical or prodromal Alzheimer's Dementia diagnosis, says Prof. Wiltfang. Blood-based differential diagnosis of dementia is gradually emerging and is expected to become a routine clinical diagnosis in the next 2-3 years.
Clinical trials and therapeutic research outlook
There is great potential for the development of optimal prophylactic treatments, including multimodal non-pharmacological prophylactic interventions. Most importantly, preventive interventions should start before the pathobiology reaches the intact neocortex.
Successful preventive interventions should start preclinically and therefore require preclinical biomarker-led diagnosis. In this regard, blood biomarkers are the most promising.
There is growing scientific evidence for the existence of subphenotypes of Alzheimer's Dementia, which are likely to respond differently to therapeutic interventions. However, subphenotype-specific preventive interventions require extensive (and expensive) clinical trials.
Non-pharmacological interventions (for example, combined lifestyle changes) or clinical trials that rely on 'drug repurposing' would not be supported by the pharmaceutical industry.
To achieve the latter in clinical trials, established gold standard biomarkers such as CSF dementia markers or amyloid PET are expensive and harmful for established preclinical diagnostics. Blood biomarkers are therefore a promising option.
A large number of studies have been reported on the mechanism of Alzheimer's Dementia, mainly focusing on amyloid β-protein (Aβ) and Tau protein.
Aβ blood test
A reduction in the Aβ 42/Aβ 40 ratio is the most validated biomarker for blood identification of Aβ peptides in Alzheimer's Dementia (AD), and Prof. Wiltfang's group has also developed a two-step immunoassay for Aβ to determine this novel ratio standard.
R . Bateman's team (USA) developed an alternative method to measure the Aβ1-42/Aβ 1-40 ratio that was approved by the US Federal Food and Drug Administration (FDA) for blood-based AD diagnosis. However, this method is expensive and difficult to establish in a routine clinical chemistry laboratory.
Early and differential detection of AD in plasma phosphorylated Tau proteins
Tau is a microtubule-associated protein (MAPT) with more than 40 phosphorylation sites. This protein is essential for axonal neuronal transport, is a major component of neurofibrillary tangles (NFTs) and is a neuropathological hallmark of AD.
High phosphorylation of Tau protein occurs in approximately 50% of cases of frontotemporal lobar degeneration (FTLD). An example is primary progressive aphasia (PPA), a manifestation of atypical Parkinson's syndrome.
Prof. Wiltfang believes that phosphorylated Tau and Aβ blood tests are expected to support early and differential diagnosis of neurodegenerative dementia. With an accuracy of at least 85% for early and differential diagnosis of AD based on phosphorylated Tau, preclinical diagnosis seems feasible. The combined application based on Aβ and phosphorylated Tau will enter the clinical routine diagnosis in the next 2-3 years.
Professor Zhu Feiqi, Director of Ward of Geriatric Cognitive Impairment, Shenzhen Luohu Hospital Group, shared Plasma high levels of Aβ1-42 had biphasic effects on peripheral monocytes and macrophages via affecting the proliferation and differentiation of hematopoietic stem cells in Alzheimer’s disease mice models.