Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Abstract

Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% -80% and 10% -20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease biomarkers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaineand amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cerebrospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

“…Also, an increase in CSF neuromodulin (GAP43), neurofilament proteins, and visinin-like protein 1 (VILIP-1) reflects degeneration that occurs in the AD brain ( 86 , 87 ). Other potential biomarkers of degeneration are α-dystroglycan, precursor of neural cell adhesion molecule 1 (NCAM-120), neuronal pentraxin receptor (NPR), cocaine- and amphetamine-regulated transcript (CART), glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) ( 88 - 90 ). Disease progression results in the alteration of many inflammatory factors in the CSF, like interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), S100 calcium-binding protein A7 (S100A7), complement C1q, interferon–γ, and markers of microglial activation: chemokine (C-C motif) ligand 2 (CCL2), triggering receptor expressed on myeloid cells 2 (TREM2), and chitotriosidase ( 5 , 83 , 91 - 94 ).…”

Neurotransmitter CART as a New Therapeutic Candidate for Parkinson’s Disease

“…This neuroprotective effect of CART has been linked to ERK activation and to the upregulation of brain-derived neurotrophic factor (BDNF) [78,79,80]. Finally, CART may be a useful biomarker for some human diseases, such as dementia with LBs, which is believed to be a syndrome in both Alzheimer’s disease and PD [81,82]. …”

Predictive Value of Cerebrospinal Fluid Visinin-Like Protein-1 Levels for Alzheimer’s Disease Early Detection and Differential Diagnosis in Patients with Mild Cognitive Impairment

“…This is complicated by the fact that the first AD symptoms occur in patients with mild cognitive impairment (MCI) of whom only 12% annually convert to AD [1]. For the proper administration of potential therapeutics, it is also important to differentiate AD from other primary causes of dementia like vascular dementia (VaD), Lewy body disease (LBD), and frontotemporal dementia (FTD) [2][3][4][5][6][7][8]. Promising AD biomarkers, such as neuroimaging and cerebrospinal fluid (CSF) biomarkers, still cannot reliably detect the disease at preclinical stages [9][10][11].…”