Sporadic Early-onset Alzheimer's Disease Research Articles

Neurons and extracellular neurofibrillary tangles in the hippocampal subdivisions in early-onset familial Alzheimer's disease: a case study.

We have investigated morphometrically unaffected neurons, intracellular neurofibrillary tangles (I-NFT) and extracellular neurofibrillary tangles (E-NFT) in eight subdivisions of the hippocampal cortex in two cases of early-onset familial Alzheimer's disease (FAD) and six cases of early-onset sporadic Alzheimer's disease (SAD). The hippocampal subdivisions examined included: CA4, CA3, CA2, CA1, prosubiculum, subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). CA3, CA2 and CA1 in the FAD cases showed more severe neuronal loss and much greater E-NFT formation than in the SAD cases, while ENT in both the FAD cases showed less neuronal loss and less E-NFT formation. These data suggest that the cornu ammonis is affected more severely than the ENT in the FAD cases. These observations indicate that hippocampal pathology in the FAD cases is qualitatively as well as quantitatively different from that in sporadic cases. These results provide further evidence for pathological heterogeneity in AD, although the number of FAD cases examined is very small.

Presenilin-1 polymorphism in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia in Japanese population.

We investigated the genetic association between intronic polymorphism in Presenilin-1 (PS-1) gene and patients with various types of dementia such as Alzheimer's disease (AD), vascular dementia (VD) and alcohol associated dementia (ALD), in Japanese population. Homozygosity for allele 1 of the PS-1 polymorphism was significantly increased in late-onset sporadic AD, but not in early-onset sporadic AD, familial AD, VD and ALD. When late-onset sporadic AD patients were divided on the basis of apolipoprotein E (APOE) genotype, homozygosity for the allele 1 of the PS-1 polymorphism was significantly increased in patients with late-onset sporadic AD without APOE epsilon 4 allele, but not in those with APOE epsilon 4 allele. Intronic mutation in PS-1 gene may be specific and one of the genetic risk factor for late-onset sporadic AD.

ApoE genotypes in Australia

We studied the apoE genotypes of 279 Australians in order to determine what relationships might exist in this group between apoE genotype and dementia associated with either early- or late-onset sporadic Alzheimer's disease (AD) or with Down's syndrome (DS). ApoE epsilon 4 allele frequency was increased in Australians with either early-onset sporadic AD (p < 0.002) or late-onset sporadic AD (p < 0.0001) and apoE epsilon 2 allele frequency was decreased in the late-onset sporadic AD group (p < 0.01). The apoE genotype distribution among patients with DS was not different from that of the control group. One individual with DS and an apoE epsilon 4/epsilon 4 genotype developed dementia at the earliest age of dementing DS patients, consistent with a role for apoE epsilon 4 in determining age of onset of dementia in AD and DS. Another DS patient with an apoE epsilon 2/epsilon 3 genotype developed dementia within an age range similar to that of four demented DS patients with an apoE epsilon 3/epsilon 3 genotype, an observation which would appear inconsistent with the proposed protective effect of apoE epsilon 2 to delay onset of dementia in DS. These results extend the evidence that the apoE genotype, particularly apoE epsilon 4, modulates dementia in early- and late-onset sporadic AD and DS. The protective role of apoE epsilon 2 in DS, however, may vary among different populations or ethnic groups.

Apolipoprotein E polymorphism in Japanese patients with Alzheimer's disease or vascular dementia.

Apolipoprotein E (ApoE) plays a key part in lipid metabolism both in the liver, and in the CNS. To clarify the association of ApoE polymorphism with Alzheimer's disease and vascular dementia in Japan, 13 patients with early onset (age > or = 65) sporadic Alzheimer's disease, 40 patients with late onset (age < or = 65) sporadic Alzheimer's disease, 19 patients with vascular dementia, and 49 non-demented control subjects were analysed. The results showed a significantly increased frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease (0.25), but not in the patients with early onset sporadic Alzheimer's disease (0.04) or in the patients with vascular dementia (0.13) compared with controls (0.09). The raised frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease was of a lower magnitude than that in United States and Canadian studies. This may in part be due to a lower epsilon 4 frequency in the normal Japanese population and reflect the lower morbidity from Alzheimer's disease in Japan.

Dose-dependent association of apolipoprotein E allele epsilon 4 with late-onset, sporadic Alzheimer's disease.

We examined the apolipoprotein E (apo E) genotypes in 47 patients with late-onset sporadic Alzheimer's disease (mean age at onset +/- standard deviation, 72.2 +/- 6.4 years), 8 with late-onset familial Alzheimer's disease (75.5 +/- 5.1 years), 18 with early-onset sporadic Alzheimer's disease (52.8 +/- 4.7 years), and 10 with early-onset familial Alzheimer's disease (52.0 +/- 6.8 years) in Japan and compared them with genotypes in control subjects. In late-onset sporadic Alzheimer's disease, apo E-epsilon 4 frequency increased significantly (epsilon 4 frequency: 0.34 vs 0.095 in controls, p < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E-epsilon 4, markedly increased with increasing dose of apo E-epsilon 4 gene (3 [95% confidence interval, 2-6] in one dose; 43 [95% confidence interval, 12-154] in two doses). This study also suggested that apo E-epsilon 4 is associated with both late-onset (epsilon 4: 0.31) and early-onset familial Alzheimer's disease (epsilon 4: 0.35). In contrast, we found no association between apo E-epsilon 4 and early-onset sporadic Alzheimer's disease (epsilon 4: 0.08). These results indicate that the risk of developing late-onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E-epsilon 4, while apo E-epsilon 4 does not appear to be a major risk factor for early-onset sporadic Alzheimer's disease.