Alzheimer’s disease (AD), which accounts for approximately 70% of dementia cases in Sweden, is a complex condition characterized by the abnormal buildup of amyloid and tau proteins. These proteins form amyloid beta (Aβ) plaques outside the cells and neurofibrillary tangles (NFTs) composed of tau protein inside the cells. Additionally, AD is often associated with cerebral amyloid angiopathy (CAA), a condition where amyloid deposits accumulate in blood vessels. Interestingly, Aβ plaques can be present in individuals without cognitive impairment, known as Cognitively Unaffected Amyloid Positive (CU-AP) individuals.
Analysis of AD Pathology Using Advanced Imaging Techniques
A recent study utilized advanced imaging techniques such as light microscopy and mass spectrometry imaging (MSI) to gain further insights into the molecular structure of AD pathology. Using Luminescent Conjugated Oligothiophenes (LCOs) and antibodies targeting phosphorylated tau (pTau) in immunohistochemistry (IHC), the researchers examined the interactions of Aβ plaques within their microenvironment in mouse models. This research identified various types of Aβ plaques, including the newly discovered coarse grain plaques, and provided information on the chemical differences between neuritic and non-neuritic cored plaques.
Hyperspectral Imaging and Tau Tracer
The study also employed hyperspectral imaging to analyze the stages of NFT maturation, revealing the sorting of tau within neurons. The binding capacity of a tau tracer molecule called GTP1 was evaluated in brain sections from sporadic AD patients. The recent approval of lecanemab, a monoclonal antibody that reduces plaques, highlights the importance of understanding the chemistry behind Aβ plaque formation and the role of tau protein.
Aβ and Tau Proteins: Crucial Factors in Cognitive Decline
There is increasing evidence that the interaction between Aβ and tau plays a significant role in cognitive decline. This research emphasizes the need for a comprehensive investigation of both Aβ plaques and NFTs to improve diagnostic and prognostic tools for AD. The development of a focused ultrasound tool, which creates openings in the blood-brain barrier to deliver medication directly to the brains of AD patients, shows promise. In initial trials on three patients, this tool led to faster plaque removal compared to traditional treatments. However, larger studies are necessary to determine potential side effects and the overall effectiveness of combining focused ultrasound with Alzheimer’s drugs.
As AD continues to pose significant challenges, advancements in diagnostic methods and treatments are of utmost importance. From proteomics analysis of cerebrospinal fluid (CSF) to identify distinct subtypes of AD to machine learning techniques exploring brain characteristics in health and disease, the field is making progress towards personalized treatment for AD. Nevertheless, more research and understanding are still needed to tackle this disease effectively.
