Cerebrospinal fluid progranulin is associated with increased cortical thickness in early stages of Alzheimer's disease

Alzheimer's disease (AD) has been linked to multiple immune system genetic variants, implicating potential broad alterations in inflammatory profiles in the disease. Triggering receptor expressed on myeloid cells 2 (TREM2) genetic variants are risk factors for AD and other neurodegenerative diseases. A soluble TREM2 isoform (sTREM2) is elevated in cerebrospinal fluid in the early stages of AD suggesting it may be a biomarker of progressive alterations in immune response to AD-related pathology. Multiple studies have reported an altered peripheral immune response in AD. However, less is known about the relationship between plasma sTREM2 and the altered peripheral immune response in AD. The objective of this exploratory study was to examine the relationship between sTREM2 and inflammatory activity in human participants defined by clinically characterized cognitive symptoms and groups defined by the cerebrospinal fluid biomarkers amyloid beta, phosphorylated tau, and neurodegeneration (NIA-AA Research Framework: "ATN continuum".) The hypothesis of this exploratory study was that sTREM2 related inflammatory activity differs by AD stage. We observed different patterns of inflammatory activity across disease groups and ATN categories that implicates peripheral sTREM2 related inflammatory activity as altered in the early stages of AD. Notably, fractalkine showed a significant relationship with sTREM2 across different analyses in the control groups that was lost as disease progressed, and fractalkine, IL-5 and IL-17A were decreased in AD. These preliminary data provide important support to the hypothesis that sTREM2-related inflammatory activity is a stage-specific biomarker of AD progression, providing the groundwork for future studies and therapeutic strategies.

Download Full-text

Cognitive and anatomical correlates of anosognosia in amnestic mild cognitive impairment and early-stage Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610216001812 ◽

2016 ◽

Vol 29 (2) ◽

pp. 293-302 ◽

Cited By ~ 8

Author(s):

Gulben Senturk ◽

Basar Bilgic ◽

Ali Bilgin Arslan ◽

Ali Bayram ◽

Hasmet Hanagasi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cortical Thickness ◽

Structural Changes ◽

Early Stage ◽

Digit Span ◽

Early Stages ◽

Amci Group

ABSTRACTBackground:Anosognosia is a common feature in Alzheimer's disease (AD). The brain substrates of anosognosia are not fully understood, and less is known about the cognitive substrates of anosognosia in prodromal and early stages of AD.Methods:Fourty-seven patients with amnestic-type mild cognitive impairment (aMCI) (n = 26) and early-stage AD (n = 21) were included, and Clinical Insight Rating Scale and Anosognosia Questionnaire for Dementia (AQ-D) were used to assess anosognosia. A detailed neuropsychological battery was administered; each patient underwent a structural magnetic resonance imaging (MRI). Correlation between anosognosia and performance in individual cognitive domains as well as correlation between anosognosia and cortical thickness values in regions of interest were assessed.Results:Performance of the anosognosic patients in Digit Ordering Test (DOT), Digit Span Backwards, and Clock Drawing Test (CDT) was significantly worse compared to non-anosognosic patients in the total study population and in the aMCI subgroup but not in AD group. AQ-D scores negatively correlated with Mini-Mental State Examination (MMSE), California Verbal Learning Test (CVLT), Digit Span Backwards and CDT scores in total group and MMSE, CVLT, DOT, and Digit Span Backwards scores in the aMCI group. No significant correlations were found between cortical thickness measurements and AQ-D scores in any of the patient populations.Conclusions:Anosognosia was associated with episodic memory, working memory, and executive functions in the total population and aMCI group, but no association was found in early-stage AD patients. Anosognosia in the early stages of AD may be related with non-structural changes such as hypoconnectivity rather than structural changes.

Download Full-text

Chemokines in CSF of Alzheimer's disease patients

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2011000400009 ◽

2011 ◽

Vol 69 (3) ◽

pp. 455-459 ◽

Cited By ~ 39

Author(s):

Jôice Dias Corrêa ◽

Daniela Starling ◽

Antônio Lúcio Teixeira ◽

Paulo Caramelli ◽

Tarcília Aparecida Silva

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Disease Progression ◽

Beta Amyloid ◽

Clinical Parameters ◽

Healthy Controls ◽

Positive Correlation ◽

Early Stages

Some studies have linked the presence of chemokines to the early stages of Alzheimer's disease (AD). Then, the identification of these mediators may contribute to diagnosis. Our objective was to evaluate the levels of beta-amyloid (BA), tau, phospho-tau (p-tau) and chemokines (CCL2, CXCL8 and CXCL10) in the cerebrospinal fluid (CSF) of patients with AD and healthy controls. The correlation of these markers with clinical parameters was also evaluated. The levels of p-tau were higher in AD compared to controls, while the tau/p-tau ratio was decreased. The expression of CCL2 was increased in AD. A positive correlation was observed between BA levels and all chemokines studied, and between CCL2 and p-tau levels. Our results suggest that levels of CCL2 in CSF are involved in the pathogenesis of AD and it may be an additional useful biomarker for monitoring disease progression.

Download Full-text

Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2015.03.001 ◽

2015 ◽

Vol 36 (6) ◽

pp. 2018-2023 ◽

Cited By ~ 49

Author(s):

Daniel Alcolea ◽

Eduard Vilaplana ◽

Jordi Pegueroles ◽

Victor Montal ◽

Pascual Sánchez-Juan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cortical Thickness

Download Full-text

Reaction-Diffusion Model of Cortical Atrophy Spread during Early Stages of Alzheimer’s Disease

10.1101/2020.11.02.362855 ◽

2020 ◽

Author(s):

Sue Kulason ◽

Michael I Miller ◽

Alain Trouvé ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diffusion Model ◽

Cortical Thickness ◽

Grey Matter ◽

Reaction Diffusion ◽

Cortical Atrophy ◽

Early Stages ◽

Reaction Diffusion Model ◽

Rhinal Cortex

1.AbstractThis study introduces a reaction-diffusion model of atrophy spread across the rhinal cortex during early stages of Alzheimer’s disease. Our finite elements model of atrophy spread is motivated by histological evidence of a spatio-temporally specific pattern of neurofibrillary tau accumulation, and evidence of grey matter atrophy correlating with sites of neurofibrillary tau accumulation. The goal is to estimate disease-related parameters such as the origin of atrophy, the speed at which atrophy spreads, and the stage of the disease. We solve a constrained optimization problem using the adjoint state method and gradient descent to match modeled cortical thickness to observed cortical thickness as calculated from 3T MRI scans. Simulation testing shows that disease-related parameters can be estimated accurately with as little as 2 years of annual observations, depending on the stage of the disease. Case studies of 3 subjects suggests that we can pinpoint the origin of atrophy to the anterior transentorhinal cortex, and that the speed of atrophy spread is less than 1 mm per year. In the future, this type of modeling could be useful to stage the progression of the disease prior to the onset of clinical symptoms.2.Author SummaryMisfolded tau proteins are associated with Alzheimer’s disease. They are known to accumulate and spread across the rhinal cortex, which is an area of the temporal lobe. Recent imaging studies suggest that we can detect grey matter thinning that occurs in pattern similar to tau spread. In this study, we introduce a model of disease spread to examine where thinning begins, how fast it spreads, and the stage of the disease. The results show that the origin of thinning corresponds with the earliest known location of tau accumulation, and spreads at a rate of less than 1 mm per year. Future work may focus on staging the progression of the disease using this type of model.

Download Full-text