Serum zonulin levels are increased in Alzheimer's disease but not in vascular dementia. 2023

Elisa Boschetti, and Giacomo Caio, and Carlo Cervellati, and Anna Costanzini, and Valentina Rosta, and Fabio Caputo, and Roberto De Giorgio, and Giovanni Zuliani
Cellular Signalling Laboratory, Department of Biomedical and Neuro Motor Sciences (DIBINEM), Institute of Human Anatomy, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy. elisa.boschetti@unibo.it.

BACKGROUND Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly. OBJECTIVE Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI). METHODS We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls. RESULTS Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders. CONCLUSIONS We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones. CONCLUSIONS Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration.

UI MeSH Term Description Entries
D011498 Protein Precursors Precursors, Protein
D006242 Haptoglobins Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16. Haptoglobin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D015140 Dementia, Vascular An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44) Arteriosclerotic Dementia,Binswanger Disease,Encephalopathy, Binswanger,Leukoencephalopathy, Subcortical,Subcortical Arteriosclerotic Encephalopathy,Vascular Dementia,Acute Onset Vascular Dementia,Arteriosclerotic Encephalopathy, Subcortical,Binswanger Encephalopathy,Binswanger's Disease,Chronic Progressive Subcortical Encephalopathy,Encephalopathy, Binswanger's,Encephalopathy, Chronic Progressive Subcortical,Encephalopathy, Subcortical Arteriosclerotic,Encephalopathy, Subcortical, Chronic Progressive,Subcortical Encephalopathy, Chronic Progressive,Subcortical Leukoencephalopathy,Subcortical Vascular Dementia,Vascular Dementia, Acute Onset,Arteriosclerotic Dementias,Arteriosclerotic Encephalopathies, Subcortical,Binswanger's Encephalopathy,Binswangers Disease,Dementia, Arteriosclerotic,Dementia, Subcortical Vascular,Dementias, Arteriosclerotic,Dementias, Subcortical Vascular,Dementias, Vascular,Disease, Binswanger,Disease, Binswanger's,Encephalopathies, Subcortical Arteriosclerotic,Encephalopathy, Binswangers,Leukoencephalopathies, Subcortical,Subcortical Arteriosclerotic Encephalopathies,Subcortical Leukoencephalopathies,Subcortical Vascular Dementias,Vascular Dementia, Subcortical,Vascular Dementias,Vascular Dementias, Subcortical
D060825 Cognitive Dysfunction Diminished or impaired mental and/or intellectual function. Cognitive Disorder,Mild Cognitive Impairment,Cognitive Decline,Cognitive Impairments,Mental Deterioration,Cognitive Declines,Cognitive Disorders,Cognitive Dysfunctions,Cognitive Impairment,Cognitive Impairment, Mild,Cognitive Impairments, Mild,Decline, Cognitive,Declines, Cognitive,Deterioration, Mental,Deteriorations, Mental,Disorder, Cognitive,Disorders, Cognitive,Dysfunction, Cognitive,Dysfunctions, Cognitive,Impairment, Cognitive,Impairment, Mild Cognitive,Impairments, Cognitive,Impairments, Mild Cognitive,Mental Deteriorations,Mild Cognitive Impairments

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