Cause of Alzheimer’s disease

The cause of Alzheimer’s disease is a question researchers are still trying to answer, but here we discuss some of the factors that may contribute.

Alzheimer’s disease (AD) was first described by Alois Alzheimer when he demonstrated increased amyloid plaques made up of amyloid beta 42 peptide (Aβ42) and neurofibrillary tangles composed of nerve cell associated protein TAU in individuals suffering from dementia.

Immunohistochemistry findings

Aβ42 and TAU proteins are quantifiable biomarkers used in diagnosing AD whereby decreased Aβ42 and increased TAU levels in the cerebrospinal fluid (CSF) are pathognomonic of AD.

Decreased Aβ42 levels in CSF have been noted in elderly people with early AD, which is also referred to as mild cognitive impairment amnestic AD. A rise in TAU levels in CSF generally followed the decline in Aβ42 in the affected patients. Thus, it has been postulated that a chronic imbalance between Aβ42 production and clearance in the brain may be a cause of Alzheimer’s disease.

Genetics

Genetic mutations and autosomal dominant inheritance patterns have been demonstrated in patients with early onset Alzheimer’s disease (inherited), unlike late onset (sporadic) AD and this supports the Aβ42 hypothesis.

Family history of the disease and presence of amyloid precursor protein (APP) and presenilin (PSEN) genes have been shown in less than one percent of AD cases.

Natural history of AD

Altered metabolism within the brain and subtle and periodic impairments of verbal memory begin a decade or two before AD symptoms. Therefore individuals destined to develop AD have detectable molecular and tissue abnormalities long before overt clinical symptoms appear.

Brain alterations occur well before AD or dementia can be diagnosed and drug interventions directed at the mild-to-moderate clinical stage may be too late to improve symptoms.

References

1. Cipriani, Gabriele; Dolciotti, Cristina; Picchi, Lucia; Bonuccelli, Ubaldo (2010-12-11). Alzheimer and his disease: a brief history. Neurological Sciences. 32 (2): 275–279.
2. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. The New England journal of medicine. 2012: 367: 795-804.
3. Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/β-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults. Archives of Neurology. 2007: 64: 343-349.
4. Jack CR, Jr., Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet neurology. 2010: 9: 119-128.
5. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green R, Olson D, Southwick P, Wolfert R, Munroe B, Lieberburg I, Seubert P, Schenk D. Reduction of β-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Annals of Neurology. 1995: 38: 643-648.
6. Bertram L, Lill CM, Tanzi RE. The genetics of Alzheimer disease: back to the future. Neuron. 2010: 68: 270-281
7. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Jr., Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2011: 7: 280-292
8. Selkoe DJ. Preventing Alzheimer’s disease. Science. 2012: 337: 1488-1492

 

Last reviewed 03/Jan/2017

Related Posts

The following two tabs change content below.
avatar

Editor

avatar

Latest posts by Editor (see all)