Skip to main content

LUP Student Papers

LUND UNIVERSITY LIBRARIES

Peripheral Immune Cell Signatures and Risk for Alzheimer’s Disease

Bali, Divya LU (2020) KIMM01 20201
Department of Immunotechnology
Educational programmes, LTH
Abstract
Alzheimer’s Disease (AD), a neurodegenerative disease, defined by abnormal accumulation of proteins, both extracellularly (senile plaques, consisting of amyloid-beta(Aβ) accumulation) and intracellularly (neurofibrillary tangles, formed by Tau protein). Several studies demonstrate that the immune cells play a central role in the pathogenesis of AD, but it is not known if immune cells from the peripheral blood are altered before the onset of AD in predisposed individuals. We tried to find out if there are any peripheral immune cell alterations in individuals without AD but with a high predisposition. For this, we used the BloodVariome cohort, which consists of genome-wide DNA sequence variant information and quantification of several immune... (More)
Alzheimer’s Disease (AD), a neurodegenerative disease, defined by abnormal accumulation of proteins, both extracellularly (senile plaques, consisting of amyloid-beta(Aβ) accumulation) and intracellularly (neurofibrillary tangles, formed by Tau protein). Several studies demonstrate that the immune cells play a central role in the pathogenesis of AD, but it is not known if immune cells from the peripheral blood are altered before the onset of AD in predisposed individuals. We tried to find out if there are any peripheral immune cell alterations in individuals without AD but with a high predisposition. For this, we used the BloodVariome cohort, which consists of genome-wide DNA sequence variant information and quantification of several immune cell types in 11731 individuals. First, we aimed to define the risk of developing AD across the BloodVariome cohort in terms of biochemical predisposition (levels of Aβ peptides in the blood) and genetic risk (polygenic risk scores). To measure the levels of Aβ, we tried to develop and optimize an immunoassay, but this was technically difficult and proved infeasible, so biochemical predisposition could not be assessed in this study. For estimating genetic risk, three different polygenic risk scores were defined and calculated. Multiple regression analysis revealed that individuals with high genetic risk tend to have increased proportions of B cells, decreased proportions of CD3+ T cells, and increased levels of CD4+CD8+ cells out of total CD3+ T cells. These results indicate that individuals with a high predisposition to AD may show specific immune cell signatures in peripheral blood. (Less)
Popular Abstract
Alzheimer’s disease (AD) is the most common form of dementia. It is an illness of the central nervous system, wherein an individual initially suffers from mild memory loss, but with the progression of AD, there is a rapid decline in language, memory, identifying people and objects, changes in mood, behavior, and personality. Age is the biggest risk factor for developing AD. The course of AD is very much influenced by the genetics. A small proportion of cases can be explained by single mutations in a single gene. But 99% of cases are due to aggregation of many genetic variations in many different genes. In AD patients' brains, there is an abnormal accumulation of proteins, mainly amyloid-beta (which accumulates outside the neurons) and tau... (More)
Alzheimer’s disease (AD) is the most common form of dementia. It is an illness of the central nervous system, wherein an individual initially suffers from mild memory loss, but with the progression of AD, there is a rapid decline in language, memory, identifying people and objects, changes in mood, behavior, and personality. Age is the biggest risk factor for developing AD. The course of AD is very much influenced by the genetics. A small proportion of cases can be explained by single mutations in a single gene. But 99% of cases are due to aggregation of many genetic variations in many different genes. In AD patients' brains, there is an abnormal accumulation of proteins, mainly amyloid-beta (which accumulates outside the neurons) and tau (which accumulates inside the neurons). These proteins can be detected in cerebrospinal fluid (the liquid that surrounds the brain and spinal cord) and are used to diagnose AD and can also be detected in the plasma. However, it is more complicated to measures these proteins in plasma.

In recent studies, several experiments demonstrate that immune cells play a role in the development of AD. But it is not known if immune cells from the peripheral blood are altered in some way before the onset of disease in the predisposed individuals.

My project aimed to find out if there are peripheral immune cell alterations in people without Alzheimer but with a high predisposition. To do that, we used a data set consisting of genetic information and peripheral immune cell levels in 11731 individuals. For each individual, we defined risk of developing AD by calculating a score representing the sum of genetic risk factors and further investigating whether individuals with high risk showed differences in immune cell levels compared to individuals with low risk. Another goal of the project was to develop an immunoassay for the measurement of amyloid-beta in plasma. (Less)
Please use this url to cite or link to this publication:
author
Bali, Divya LU
supervisor
organization
course
KIMM01 20201
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Alzheimer's Disease, Polygenic Risk Score, ELISA, Immune cell alterations
language
English
id
9012230
date added to LUP
2020-06-03 09:45:55
date last changed
2020-06-03 09:45:55
@misc{9012230,
  abstract     = {{Alzheimer’s Disease (AD), a neurodegenerative disease, defined by abnormal accumulation of proteins, both extracellularly (senile plaques, consisting of amyloid-beta(Aβ) accumulation) and intracellularly (neurofibrillary tangles, formed by Tau protein). Several studies demonstrate that the immune cells play a central role in the pathogenesis of AD, but it is not known if immune cells from the peripheral blood are altered before the onset of AD in predisposed individuals. We tried to find out if there are any peripheral immune cell alterations in individuals without AD but with a high predisposition. For this, we used the BloodVariome cohort, which consists of genome-wide DNA sequence variant information and quantification of several immune cell types in 11731 individuals. First, we aimed to define the risk of developing AD across the BloodVariome cohort in terms of biochemical predisposition (levels of Aβ peptides in the blood) and genetic risk (polygenic risk scores). To measure the levels of Aβ, we tried to develop and optimize an immunoassay, but this was technically difficult and proved infeasible, so biochemical predisposition could not be assessed in this study. For estimating genetic risk, three different polygenic risk scores were defined and calculated. Multiple regression analysis revealed that individuals with high genetic risk tend to have increased proportions of B cells, decreased proportions of CD3+ T cells, and increased levels of CD4+CD8+ cells out of total CD3+ T cells. These results indicate that individuals with a high predisposition to AD may show specific immune cell signatures in peripheral blood.}},
  author       = {{Bali, Divya}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Peripheral Immune Cell Signatures and Risk for Alzheimer’s Disease}},
  year         = {{2020}},
}