Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.
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http://dx.doi.org/10.3390/jpm10030061 | DOI Listing |
Mol Neurodegener
January 2025
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry.
View Article and Find Full Text PDFFluids Barriers CNS
January 2025
Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, 760 Press Ave, 124 HKRB, Lexington, KY, 40536-0679, USA.
Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.
Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.
Alzheimers Res Ther
January 2025
Laboratory for Clinical Neuroscience, Center for Biomedical Technology, Universidad Politécnica de Madrid, IdISSC, Crta M40, km38, Madrid, 28223, Spain.
Background: Dementia patients commonly present multiple neuropathologies, worsening cognitive function, yet structural neuroimaging signatures of dementia have not been positioned in the context of combined pathology. In this study, we implemented an MRI voxel-based approach to explore combined and independent effects of dementia pathologies on grey and white matter structural changes.
Methods: In 91 amnestic dementia patients with post-mortem brain donation, grey matter density and white matter hyperintensity (WMH) burdens were obtained from pre-mortem MRI and analyzed in relation to Alzheimer's, vascular, Lewy body, TDP-43, and hippocampal sclerosis (HS) pathologies.
Commun Biol
January 2025
Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
Brain organoid models have greatly facilitated our understanding of human brain development and disease. However, key brain cell types, such as microglia, are lacking in most brain organoid models. Because microglia have been shown to play important roles in brain development and pathologies, attempts have been made to add microglia to brain organoids through co-culture.
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