Abstract
Apolipoprotein E (Apo E) genotype is a genetic risk factor influencing the development of Alzheimer's disease (AD).Progressive supranuclear palsy (PSP), like AD, is a dementing illness with neurofibrillary tangles. We determined the frequencies of Apo E alleles in 52 PSP patients and 52 age- and gender-matched controls. The distribution of Apo E allele frequencies and genotypes showed no difference between PSP and controls. Apo E allele status does not influence the development of PSP.
NEUROLOGY 1996;46: 1156-1157
The epsilon 4 allele of apolipoprotein E gene (ApoE) affects the risk and age of onset of Alzheimer's disease (AD). [1,2] ApoE epsilon 4 is overrepresented in the Lewy body variant of AD, [3] but not in Parkinson's disease with or without dementia, [4] or in alcoholic dementia. [5] It is not known whether ApoE genotype is important in other dementing neurodegenerative diseases. Progressive supranuclear palsy (PSP) is a dementing neurodegenerative condition characterized pathologically by neurofibrillary tangles. [6] Strittmatter et al. [7] suggested that increased neurofibrillary protein deposition in neuronal tangles is a mechanism underlying ApoE epsilon 4 effects in AD. Therefore, we determined ApoE genotypes in PSP to assess its role in this disease.
Methods.
Subjects.
Patients with PSP were recruited from movement disorder clinics at the University of Kansas, the Toronto Hospital, Buffalo Veterans Affairs Medical Center, and Robert Wood Johnson Medical School. PSP was diagnosed clinically by the presence of bradykinesia, rigidity with axial predominance, and supranuclear disorder of ocular motility with definite down-gaze palsy. The course had to be progressive, and responsiveness to levodopa minimal and not sustained. Patients with clinical features of multiple system atrophy or other causes of secondary parkinsonism were excluded. Controls were age- and gender-matched volunteers participating in a longitudinal study of aging at the University of Kansas.
Genotyping.
Genomic DNA was prepared from white cell pellets and extracted with phenol and chloroform. ApoE genotypes were determined in duplicate without knowledge of subject's clinical status using primers, polymerase chain reaction conditions, and the restriction digest method previously described. [8]
Statistics.
The chi-square test was used for initial tests of potential differences in ApoE allele and genotype frequencies between PSP and controls.
Results.
There were 32 men and 20 women in the PSP and control groups. The average duration of disease was 3.6 plus minus 3.3 years (range 1 to 14 years). The mean age for the PSP patients was 71.0 plus minus 6.4 years (range 58 to 86 years) and for controls the mean age was 70.9 plus minus 6.8 (range 55 to 85 years), which was not statistically different. There was no difference between the distribution of ApoE alleles in PSP and controls, and the distribution of ApoE genotypes in PSP and controls Table 1.
Table 1. Distribution of Apo E genotypes and alleles in PSP and controls
Discussion.
Han et al. [9] hypothesized that the physiologic function of ApoE is to contribute to the stabilization of neuronal microtubule integrity by binding and sequestering free tau. PSP is characterized clinically by cognitive impairment, ophthalmoplegia, postural instability, dysarthria, and an akinetic-rigid syndrome. [10] The neuropsychological profile of early PSP, unlike that of AD, is characterized by severe frontal lobe symptoms with a relative sparing of language and memory. [11,12] As the disease progresses, there is a more global and severe deterioration of intellectual functioning. Numerous neurofibrillary tangles or neurophilic threads in the basal ganglia and brainstem are necessary for the pathologic diagnosis. [13] Even though neurofibrillary tangles in PSP are tau positive, they differ from those in AD by being composed of straight (not helical) filaments. [14]
A conclusive association for ApoE genotype and dementia has been shown only for AD. Frisoni et al. [15] found that the frequency of the epsilon 4 allele was as high in vascular dementia (0.46) as in AD (0.45), but Pirtilla et al. [16] found a high frequency in mixed dementia (0.42), but not in probable vascular dementia (0.21). Our findings indicate that ApoE genotype is not a susceptibility factor for PSP. Preliminary results indicate that ApoE genotype is also not important in the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, a dementing illness with widespread tangle formation. [17] These findings suggest that other dementias associated with neurofibrillary tangle formation may have a pathogenic mechanism different from those involved in ApoE related AD.
- Copyright 1996 by Advanstar Communications Inc.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Hastening the Diagnosis of Amyotrophic Lateral Sclerosis
Dr. Brian Callaghan and Dr. Kellen Quigg
► Watch
Alert Me
Recommended articles
The apolipoprotein E epsilon 4 allele is associated with increased neuritic plaques and cerebral amyloid angiopathy in Alzheimer's disease and Lewy body variant
APOE E4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy
APOE and the risk of PD with or without dementia in a population-based study
APOE ε4 is associated with severity of Lewy body pathology independent of Alzheimer pathology