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Biomedical subjects

T D Bird

Publications and source records attributed to T D Bird.

At least 91 records · Page 5Linked to original sources
PubMed1996

Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.

To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0001), PS2N1411 (P = 0.009), APPK670N,M671L (P < 0.0001), and APPV7171 (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.

Alzheimer Disease↗
PubMed1996

Mapping of hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) to distal chromosome 17q.

Hereditary neuralgic amyotrophy with predilection for the brachial plexus (HNA) is an autosomal dominant disorder associated with recurrent, episodic, painful brachial neuropathies. Mildly dysmorphic facial features, including hypotelorism, long nasal bridge, and upslanting palpebral fissures, are present in affected persons in some pedigrees with HNA. To determine the chromosomal location of the HNA gene, we carried out genetic linkage studies with polymerase chain reaction-based DNA markers in two large pedigrees. Linkage to markers from the distal long arm of chromosome 17 was established.

Adult↗
PubMed1996

Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women.

Late-onset Alzheimer disease (AD) is associated with the apolipoprotein E (APOE)-epsilon4 allele. In late-onset familial AD, women have a significantly higher risk of developing the disease than do men. The aim of this study was to determine whether the gender difference in familial AD is a function of APOE genotype. We studied 58 late-onset familial AD kindreds. Kaplan-Meier survival analysis was used to assess genotype-specific distributions of age at onset. Odds ratios were estimated by logistic regression with adjustment for age and by conditional logistic regression with stratification on families. All methods detected a significant gender difference for the epsilon4 heterozygous genotype. In women, epsilon4 heterozygotes had higher risk than those without epsilon4; there was no significant difference between epsilon4 heterozygotes and epsilon4 homozygotes. In men, epsilon4 heterozygotes had lower risk than epsilon4 homozygotes; there was not significant difference between epsilon4 heterozygotes and those without epsilon4. A direct comparison of epsilon4 heterozygous men and women revealed a significant twofold increased risk in women. We confirmed these results in 15 autopsy-confirmed AD kindreds from the National Cell Repository at Indiana University Alzheimer Disease Center. These observations are consistent with the increased incidence of familial AD in women and may be a critical clue to the role of gender in the pathogenesis of AD.

Age of Onset↗
PubMed1996

Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease.

Mutations in the presenilin (PS)-1 and PS-2 genes have been shown to be linked with the development of Alzheimer's disease (AD). We examined Alzheimer's brain tissue by immunohistochemistry using a set of antibodies raised to sequences shared between PS-1 and PS-2 proteins. These antibodies reacted exclusively with a subset of neurofibrillary tangles and not with neuropil threads or dystrophic neurites. Detection of the presenilin epitope in neurofibrillary tangles was observed in sporadic Alzheimer's disease brain samples and in samples from individuals carrying PS-1 and PS-2 mutations with no qualitative difference. These data indicate that both wild-type and mutant PS proteins are involved in a common pathogenic pathway in AD.

Alzheimer Disease↗
PubMed1995

A familial Alzheimer's disease locus on chromosome 1.

The Volga German kindreds are a group of seven related families with autosomal dominant early-onset Alzheimer's disease (AD). Linkage to known AD-related loci on chromosomes 21 and 14 has been excluded. Significant evidence for linkage to AD in these families was obtained with D1S479 and there was also positive evidence for linkage with other markers in the region. A 112-base pair allele of D1S479 co-segregated with the disease in five of seven families, which is consistent with a common genetic founder. This study demonstrates the presence of an AD locus on chromosome 1q31-42.

Adult↗
PubMed1995

Why do DNA testing? Practical and ethical implications of new neurogenetic tests.

Direct DNA tests for mutations in neurogenetic disorders are establishing a new era in diagnostic neurology. These highly accurate and specific tests will greatly improve diagnosis and genetic counseling, lead to more accurate assessment of prognosis, and reduce the cost of diagnostic evaluations. However, the use and interpretation of the tests can be complicated, and there are numerous social, psychological, and ethical implications of the testing that need to be recognized and anticipated. To provide the best care for our patients, neurologists need to understand the benefits and risks of this testing and properly apply it in the context of each individual clinical situation.

Ethics↗
PubMed1995

Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease.

The effect of the apolipoprotein E (APOE) epsilon 4 allele on age of onset was analyzed in two groups of families with early-onset Alzheimer's disease (AD), (1) Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2) early-onset non-VG families showing evidence of linkage to chromosome 14. The epsilon 4 allele did not have a detectable effect on age of onset in either group. This finding suggests some forms of early-onset familial AD are not modifiable by APOE status, or that AD can be caused by APOE-independent pathways.

Age of Onset↗
PubMed1995

Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia.

The ataxias are a complex group of diseases with both environmental and genetic causes. Among the autosomal dominant forms of ataxia the genes for two, spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD), have been isolated. In both of these disorders the molecular basis of disease is the expansion of an unstable CAG trinucleotide repeat. To assess the frequency of the SCA1 and MJD trinucleotide repeat expansions among individuals diagnosed with ataxia we have collected DNA from individuals representing 311 families with adult-onset ataxia of unknown etiology and screened these samples for trinucleotide repeat expansions within the SCA1 and MJD genes. Within this group there are 149 families with dominantly inherited ataxia. Of these, 3% had SCA1 trinucleotide repeat expansions, whereas 21% were positive for the MJD trinucleotide expansion. Thus, together SCA1 and MJD represent 24% of the autosomal dominant ataxias in our group, and the frequency of MJD is substantially greater than that of SCA1. For the 57 patients with MJD trinucleotide repeat expansions, a strong inverse correlation between CAG repeat size and age at onset was observed (r = -.838). Among the MJD patients, the normal and affected ranges of CAG repeat size are 14-40 and 68-82 repeats, respectively. For SCA1 the normal and affected ranges are much closer, containing 19-38 and 40-81 CAG repeats, respectively.

Adult↗
PubMed1994

Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis.

We describe two kindreds with an autosomal dominant inherited disorder characterized by a variable degree of muscle weakness of limbs, vocal cords, and intercostal muscles and by asymptomatic sensory loss, beginning in infancy or childhood in severely affected persons. Life expectancy in severely affected patients is shortened because of respiratory failure. Because nerve conduction velocities are normal and it is an inherited axonal neuropathy, we classify the disorder as a variety of hereditary motor and sensory neuropathy type II (HMSN II) (HMSN IIc). The present report provides further evidence for heterogeneity among the hereditary motor and sensory neuropathy type II disorders. In one large pedigree with the type IIc disorder, no linkage to DNA markers known to map near the HMSN IA locus on chromosome 17p or the HMSN IB locus on chromosome 1q was demonstrated.

Adolescent↗
PubMed1994

Phenotype of chromosome 14-linked familial Alzheimer's disease in a large kindred.

We report the clinical and neuropathological features of chromosome 14-linked familial Alzheimer's disease (14qFAD) in affected members of the L family. Some clinical information on all 16 known affected individuals and detailed neuropathological findings in 6 family members were available for review. Common features of the phenotype of 14qFAD in the L family included onset of dementia before the age of 50, early progressive aphasia, early-appearing myoclonus and generalized seizures, paratonia, cortical atrophy, numerous and extensive senile plaques and neurofibrillary tangles, and prominent amyloid angiopathy. Descriptions of phenotypic features were available for six additional recently defined 14q-linked FAD kindreds: the findings in four of them (FAD4, FAD2, A, B) indicated a relatively consistently shared 14qFAD phenotype, conforming closely with the specific clinical and neuropathological characteristics noted in the L family. Comparisons also suggested several ostensible phenotypic variants in 14qFAD: (1) In two 14q-linked kindreds (SNW/FAD3, FAD1), affected individuals in some instances were noted to survive to age 70 or beyond and the mean age at onset (> 49 years) in these two kindreds was somewhat higher than in their five 14qFAD counterparts (< 48 years in each); (2) in the SNW/FAD3 kindred, seizures and myoclonus were absent in all 10 subjects examined; and (3) cerebellar amyloid plaques were variably present within and among several 14qFAD kindreds. Comparisons with phenotypic features recently detailed in three kindreds (TOR3, F19, ROM) with codon 717 amyloid precursor protein gene mutations (i.e., APP717 FAD) suggested several distinctions: Prominent progressive aphasia, myoclonus, seizures, and paratonia were all apparently less prevalent in APP717 FAD, with language function predominantly spared over the initial disease course. The extent of homogeneity and heterogeneity in the clinical and neuropathological phenotype of 14q-linked FAD and its possible meaningful distinctions from the phenotypes of APP717 FAD await further determination.

Adult↗
PubMed1994

Major patterns of human inheritance: relevance to the epilepsies.

An understanding of the basic principles of human inheritance patterns is necessary to appreciate the variety and complexity of genetic influences in the epilepsies. The various modes of human inheritance include single gene (mendelian), chromosomal, mitochondrial, and multifactorial/polygenic. Recent insights regarding imprinting, anticipation, and uniparental disomy have been made and have an impact on our understanding of human genetics. All of these phenomena are likely to be of importance in the epilepsies and form the basis for a more detailed analysis of the relevant molecular biology.

Child↗
PubMed1994

Impotence associated with the Charcot-Marie-Tooth syndrome.

We report 7 men (ages 45-61 years) with impotence associated with the Charcot-Marie-Tooth syndrome (CMT). The range of onset of erectile dysfunction varied from 38 to 55 years of age. One patient had classic CMT 1A with autosomal dominant inheritance, slow motor nerve conduction velocities and the 17p DNA duplication. One had probable type-II hereditary motor and sensory neuropathy. None of the patients had diabetes. There was some benefit from papaverine injection therapy or penile implants. The association of impotence with CMT is likely to be more common than previously recognized.

Adult↗