Tags

Type your tag names separated by a space and hit enter

Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life.
Arch Neurol. 2005 Dec; 62(12):1821-30.AN

Abstract

BACKGROUND

Cases of early-onset Alzheimer disease (AD) with an autosomal dominant inheritance pattern (familial AD [FAD]) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, <40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD.

OBJECTIVE

To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life.

DESIGN, SETTING, AND PARTICIPANTS

The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer's Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD.

RESULTS

Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F) in exon 6 of the PSEN1 gene, which segregates with disease.

CONCLUSIONS

A novel PSEN1 mutation causes very-early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.

Authors+Show Affiliations

Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA. sniderj@neuro.wustl.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16344340

Citation

Snider, B Joy, et al. "Novel Presenilin 1 Mutation (S170F) Causing Alzheimer Disease With Lewy Bodies in the Third Decade of Life." Archives of Neurology, vol. 62, no. 12, 2005, pp. 1821-30.
Snider BJ, Norton J, Coats MA, et al. Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life. Arch Neurol. 2005;62(12):1821-30.
Snider, B. J., Norton, J., Coats, M. A., Chakraverty, S., Hou, C. E., Jervis, R., Lendon, C. L., Goate, A. M., McKeel, D. W., & Morris, J. C. (2005). Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life. Archives of Neurology, 62(12), 1821-30.
Snider BJ, et al. Novel Presenilin 1 Mutation (S170F) Causing Alzheimer Disease With Lewy Bodies in the Third Decade of Life. Arch Neurol. 2005;62(12):1821-30. PubMed PMID: 16344340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life. AU - Snider,B Joy, AU - Norton,Joanne, AU - Coats,Mary A, AU - Chakraverty,Sumi, AU - Hou,Craig E, AU - Jervis,Ramiro, AU - Lendon,Corinne L, AU - Goate,Alison M, AU - McKeel,Daniel W,Jr AU - Morris,John C, PY - 2005/12/14/pubmed PY - 2006/1/21/medline PY - 2005/12/14/entrez SP - 1821 EP - 30 JF - Archives of neurology JO - Arch Neurol VL - 62 IS - 12 N2 - BACKGROUND: Cases of early-onset Alzheimer disease (AD) with an autosomal dominant inheritance pattern (familial AD [FAD]) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, <40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD. OBJECTIVE: To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life. DESIGN, SETTING, AND PARTICIPANTS: The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer's Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD. RESULTS: Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F) in exon 6 of the PSEN1 gene, which segregates with disease. CONCLUSIONS: A novel PSEN1 mutation causes very-early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/16344340/Novel_presenilin_1_mutation__S170F__causing_Alzheimer_disease_with_Lewy_bodies_in_the_third_decade_of_life_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.62.12.1821 DB - PRIME DP - Unbound Medicine ER -