Dementia of the Alzheimer type

Nee, Le; Eldridge, Roswell; Sunderland, Trey; Thomas, Cheryl; Katz, Diane; Thompson, K.; Weingartner, Herbert; Weiss, Howard D.; Julian, Colleen G.; Cohen, Richard L.

doi:10.1212/wnl.37.3.359

Cited by 127 publications

(30 citation statements)

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“…Age at onset of AD in two of these case reports (age of onset 3414 and 50 years16) raises the possibility that specific genetic mutations could have been responsible for the disease. Other reports of neuropathology in affected twins have included only one autopsy per twin pair17 or have not commented on neuropathology details 10. We are unaware of any case reports of autopsies in both twins of a MZ pair with a PS1 mutation.…”

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confidence: 99%

Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease

Brickell

Leverenz

Steinbart

et al. 2007

Journal of Neurology, Neurosurgery & Psychiatry

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Aim: Neuropathological examination of both individuals in a monozygotic (MZ) twin pair with Alzheimer's disease (AD) is rare, especially in the molecular genetic era. We had the opportunity to assess the concordance and discordance of clinical presentation and neuropathology in three MZ twin pairs with AD. Methods: The MZ twins were identified and characterised by the University of Washington Alzheimer's Disease Research Center. We reviewed the available clinical and neuropathological records for all six cases looking specifically for concordance and discordance of clinical phenotype, neuritic amyloid plaques (NP), neurofibrillary tangles (NFT) and Lewy related pathology (LRP). Results: Discordance in age of onset for developing AD in the MZ twins varied from 4 to 18 years. Clinical presentations also differed between twins. One twin presented with a dementia with Lewy Body clinical syndrome while the other presented with typical clinical AD. Neuropathology within the MZ twin pairs was concordant for NP and NFT, regardless of duration of disease, and was discordant for LRP. This difference was most marked in the late onset AD twin pair. One pair was found to have a mutation in presenilin-1 (PS1) (A79V) with remarkably late onset in a family member. Conclusions: MZ twins with AD can vary considerably in age of onset, presentation and disease duration. The concordance of NP and NFT pathological change and the discordance of LRP support the concept that, in AD, the former are primarily under genetic control whereas the latter (LRP) is more influenced by disease duration and environmental factors. The A79V mutation in PS1 can be associated with very late onset of dementia. A lzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia in the elderly. AD has typically been divided into early onset (EOAD, onset ,60 years) and late onset (LOAD, onset >60 years). LOAD occurs in the majority (.95%) of patients with AD 1 while EOAD accounts for a small proportion of patients (,5%). Demarcation of familial LOAD/EOAD is not absolute as approximately 25% of families with familial LOAD will have members with EOAD, accounting for about 6% of all affected cases. 2The cause of AD is unknown in the majority of cases. The most powerful risk factors for developing LOAD are age, a positive family history and APOE genotype. Specific mendelian genetic factors have also been identified in patients who develop familial EOAD, namely mutations in presenilin 1 (PS1), 4 presenilin 2 (PS2) 5 and amyloid precursor protein.6 PS1 mutations are the most frequent pathogenic mutation in EOAD. 7 Genetic variation influences a number of aspects of clinical phenotype in patients affected by AD, 1 with modelling suggesting that environmental factors are also important in determining development of dementia.8 Monozygotic (MZ) twins provide a unique insight into the relationship between genetic programming and environmental factors impacting on that programming. Twin studies suggest a polygenic multifactorial mode of inheritanc...

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confidence: 99%

Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease

Brickell

Leverenz

Steinbart

et al. 2007

Journal of Neurology, Neurosurgery & Psychiatry

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“…Monozygotic twin studies indicate a variable concordance of between 18% 15 and 41%, 16 showing that Alzheimer's disease cannot be explained completely by a single autosomal dominant gene. A relative risk of 3.5 has been demonstrated for those with at least one first degree relative suVering from dementia.…”

Section: Genetics Of Alzheimer's Diseasementioning

confidence: 99%

Genetic risk factors in Alzheimer's disease

Tilley

Morgan

Kalsheker

1998

Molecular Pathology

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Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease. (J Clin Pathol: Mol Pathol 1998;51:293-304)

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“…Tubular plugging by crystal laden tubular cells was found in renal tissue, although the crystals were not positively identified as containing triamterene or a metabolite.6 Nevertheless, only one definite case of interstitial nephritis induced by triamterene has been reported. 7 The presence of triamterene in a calculus may be suspected by blue fluorescence (440 nm) under long wave ultraviolet light, but thin layer chromatography8 or infrared spectroscopy provides definitive analysis.' The composition of the stones varies: half of 66 stones containing triamterene were found to contain less than 5% and none contained more than 75% of material derived from the drug.8 Triamterene itself, rather than its more abundant metabolites, was the commonest constituent.…”

Section: Reforming Health Care In the United Statesmentioning

confidence: 99%