What causes alzheimer's disease?

Richard A. Armstrong

Research output: Contribution to journalArticle

Abstract

Since the earliest descriptions of Alzheimer's disease (AD), many theories have been advanced as to its cause. These include: (1) exacerbation of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3) an environmental factor such as exposure to aluminium, head injury, or malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes and allelic variation in apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these theories and concludes that AD is a multifactorial disorder in which genetic and environmental risk factors interact to increase the rate of normal aging ('allostatic load'). The consequent degeneration of neurons and blood vessels results in the formation of abnormally aggregated 'reactive' proteins such as ß-amyloid (Aß) and tau. Gene mutations influence the outcome of age-related neuronal degeneration to cause early onset familial AD (EO-FAD). Where gene mutations are absent and a combination of risk factors present, Aß and tau only slowly accumulate not overwhelming cellular protection systems until later in life causing late-onset sporadic AD (LO-SAD). Aß and tau spread through the brain via cell to cell transfer along anatomical pathways, variation in the pathways of spread leading to the disease heterogeneity characteristic of AD.
Original languageEnglish
Pages (from-to)169-188
Number of pages20
JournalFolia Neuropathologica
Volume51
Issue number3
DOIs
Publication statusPublished - 31 Dec 2013

Fingerprint

Alzheimer Disease
Mutation
Allostasis
Presenilins
Genes
Nerve Degeneration
Amyloid beta-Protein Precursor
Blood-Brain Barrier
Aluminum
Craniocerebral Trauma
Amyloid
Malnutrition
Cholinergic Agents
Blood Vessels
Immune System
Brain
Proteins

Bibliographical note

Creative Commons Attribution Non-Commercial Share Alike International 4.0

Keywords

  • Alzheimer's disease
  • aetiology
  • aging
  • genetic factors
  • beta-amyloid
  • tau

Cite this

Armstrong, Richard A. / What causes alzheimer's disease?. In: Folia Neuropathologica. 2013 ; Vol. 51, No. 3. pp. 169-188.
@article{45a67feb66a14b12a8a94859ba2b4e8b,
title = "What causes alzheimer's disease?",
abstract = "Since the earliest descriptions of Alzheimer's disease (AD), many theories have been advanced as to its cause. These include: (1) exacerbation of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3) an environmental factor such as exposure to aluminium, head injury, or malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes and allelic variation in apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these theories and concludes that AD is a multifactorial disorder in which genetic and environmental risk factors interact to increase the rate of normal aging ('allostatic load'). The consequent degeneration of neurons and blood vessels results in the formation of abnormally aggregated 'reactive' proteins such as {\ss}-amyloid (A{\ss}) and tau. Gene mutations influence the outcome of age-related neuronal degeneration to cause early onset familial AD (EO-FAD). Where gene mutations are absent and a combination of risk factors present, A{\ss} and tau only slowly accumulate not overwhelming cellular protection systems until later in life causing late-onset sporadic AD (LO-SAD). A{\ss} and tau spread through the brain via cell to cell transfer along anatomical pathways, variation in the pathways of spread leading to the disease heterogeneity characteristic of AD.",
keywords = "Alzheimer's disease, aetiology, aging, genetic factors, beta-amyloid, tau",
author = "Armstrong, {Richard A.}",
note = "Creative Commons Attribution Non-Commercial Share Alike International 4.0",
year = "2013",
month = "12",
day = "31",
doi = "10.5114/fn.2013.37702",
language = "English",
volume = "51",
pages = "169--188",
journal = "Folia Neuropathologica",
issn = "1641-4640",
publisher = "Polish Association of Neuropathologists",
number = "3",

}

What causes alzheimer's disease? / Armstrong, Richard A.

In: Folia Neuropathologica, Vol. 51, No. 3, 31.12.2013, p. 169-188.

Research output: Contribution to journalArticle

TY - JOUR

T1 - What causes alzheimer's disease?

AU - Armstrong, Richard A.

N1 - Creative Commons Attribution Non-Commercial Share Alike International 4.0

PY - 2013/12/31

Y1 - 2013/12/31

N2 - Since the earliest descriptions of Alzheimer's disease (AD), many theories have been advanced as to its cause. These include: (1) exacerbation of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3) an environmental factor such as exposure to aluminium, head injury, or malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes and allelic variation in apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these theories and concludes that AD is a multifactorial disorder in which genetic and environmental risk factors interact to increase the rate of normal aging ('allostatic load'). The consequent degeneration of neurons and blood vessels results in the formation of abnormally aggregated 'reactive' proteins such as ß-amyloid (Aß) and tau. Gene mutations influence the outcome of age-related neuronal degeneration to cause early onset familial AD (EO-FAD). Where gene mutations are absent and a combination of risk factors present, Aß and tau only slowly accumulate not overwhelming cellular protection systems until later in life causing late-onset sporadic AD (LO-SAD). Aß and tau spread through the brain via cell to cell transfer along anatomical pathways, variation in the pathways of spread leading to the disease heterogeneity characteristic of AD.

AB - Since the earliest descriptions of Alzheimer's disease (AD), many theories have been advanced as to its cause. These include: (1) exacerbation of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3) an environmental factor such as exposure to aluminium, head injury, or malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes and allelic variation in apolipoprotein E (Apo E), (5) mitochondrial dysfunction, (6) a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these theories and concludes that AD is a multifactorial disorder in which genetic and environmental risk factors interact to increase the rate of normal aging ('allostatic load'). The consequent degeneration of neurons and blood vessels results in the formation of abnormally aggregated 'reactive' proteins such as ß-amyloid (Aß) and tau. Gene mutations influence the outcome of age-related neuronal degeneration to cause early onset familial AD (EO-FAD). Where gene mutations are absent and a combination of risk factors present, Aß and tau only slowly accumulate not overwhelming cellular protection systems until later in life causing late-onset sporadic AD (LO-SAD). Aß and tau spread through the brain via cell to cell transfer along anatomical pathways, variation in the pathways of spread leading to the disease heterogeneity characteristic of AD.

KW - Alzheimer's disease

KW - aetiology

KW - aging

KW - genetic factors

KW - beta-amyloid

KW - tau

UR - http://www.termedia.pl/Review-article-What-causes-alzheimer-s-disease-,20,21432,0,1.html

U2 - 10.5114/fn.2013.37702

DO - 10.5114/fn.2013.37702

M3 - Article

VL - 51

SP - 169

EP - 188

JO - Folia Neuropathologica

JF - Folia Neuropathologica

SN - 1641-4640

IS - 3

ER -