SORL1 gene mutation and octapeptide repeat insertion in PRNP gene in a case presenting with rapidly progressive dementia and cerebral amyloid angiopathy.
Aged, 80 and over
Alzheimer Disease
/ complications
Amyloid beta-Peptides
/ cerebrospinal fluid
Cerebral Amyloid Angiopathy
/ complications
Dementia
/ complications
Humans
LDL-Receptor Related Proteins
/ genetics
Male
Membrane Transport Proteins
/ genetics
Mutation
Myoclonus
Prion Proteins
/ genetics
tau Proteins
/ cerebrospinal fluid
Alzheimer's disease
PRNP gene
SORL1 gene
cerebral amyloid angiopathy
prion diseases
rapidly progressive Alzheimer disease
rapidly progressive dementia
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
12
05
2022
accepted:
29
06
2022
pubmed:
6
7
2022
medline:
12
10
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80-year-old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the PRNP and SORL1 genes. Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic-electromyographic (EEG-EMG) polygraphy, and analysis of 14-3-3 and tau proteins, Aβ40, and Aβ42 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis. The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9 months after symptom onset, he was bed-bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t-tau and p-tau, decreased Aβ42, decreased Aβ42/Aβ40 ratio, and absence of 14.3.3 protein. EEG-EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike-waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the SORL1 gene and the presence of a single octapeptide repeat insertion in the coding region of the PRNP gene. The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.
Sections du résumé
BACKGROUND AND PURPOSE
Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80-year-old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the PRNP and SORL1 genes.
METHODS
Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic-electromyographic (EEG-EMG) polygraphy, and analysis of 14-3-3 and tau proteins, Aβ40, and Aβ42 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis.
RESULTS
The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9 months after symptom onset, he was bed-bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t-tau and p-tau, decreased Aβ42, decreased Aβ42/Aβ40 ratio, and absence of 14.3.3 protein. EEG-EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike-waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the SORL1 gene and the presence of a single octapeptide repeat insertion in the coding region of the PRNP gene.
CONCLUSIONS
The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.
Substances chimiques
Amyloid beta-Peptides
0
LDL-Receptor Related Proteins
0
Membrane Transport Proteins
0
PRNP protein, human
0
Prion Proteins
0
SORL1 protein, human
0
tau Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3139-3146Informations de copyright
© 2022 European Academy of Neurology.
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