PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea

Figures & data

Figure 1 Neuroimaging data.

Notes: T2-Fluid attenuated inversion recover images of brain magnetic resonance images taken 2 years after the symptom onset demonstrate diffuse cortical atrophy, more severe in the bilateral parietal lobes (A–D). 18F-Fluorodeoxyglucose positron emission tomography demonstrates a marked hypometabolism in the bilateral temporoparietal areas (E–H). A follow-up computed tomography taken 6 years after the onset showed a marked atrophy in whole brain (I–L).

Figure 2 Data of genetic analysis for the AD patient with PSEN1 L226F.

Notes: (A) SSCP data of patient with L226F mutation, located at position 2 (2*). Numbers 1, 3, and 4 are wild-type samples (B). Sequencing data of PSEN1 L226F. (C) Location of L226F in PSEN1 protein.
Abbreviations: SSCP, single strand conformation polymorphism; AD, Alzheimer’s disease.

Figure 3 3D structure prediction for PSEX1 protein with L226F mutation, comparing to the normal PSEN1 protein.

Abbreviation: 3D, three dimensional.

Table 1 Comparisons of dominant features of patients with PSEN1 L226F

Case	Zekanowski et al (2006)^Citation25	Gomez-Tortosa et al (2010)^Citation27	Korean patient
Age of onset	33 years	33 years	37 years
Family history	Yes; mother, clinical YOD	Yes; father, clinical YOD	None
Symptoms	Early behavioral, frontal signs, subsequent severe recent memory loss, mild parkinsonism, progress to mutism	Early depression, dysarthria, nonfluent aphasia, cognitive declines, subsequent Parkinsonism	Early paranoid ideation and anxiety, cognitive decline, nonfluent aphasia progress to mutism, late Parkinsonism
Neuroimaging characteristics	Frontal atrophy on CT; severe hypoperfusion in frontal areas on SPECT	Diffuse cortical atrophy on MRI	Diffuse cortical atrophy on MRI; marked cortical hypometabolism especially in bilateral parietal regions on FDG-PET
Age of death	38 years	42 years	44 years
Autopsy	AD pathology	AD pathology	Not done

Abbreviations: AD, Alzheimer’s disease; CT, computerized tomography; FDG-PET, fluorodeoxyglucose glucose positron emission tomography; MRI, magnetic resonance imaging; YOD, young-onset dementia.

Table 2 Comparisons of the distinct characteristics between the patients with PSEN1, L226F, and L226R

Case	L226F (Zekanowski et al [2006];^Citation25 Gomez-Tortosa et al [2010];^Citation27 this case)	L226R (Coleman et al [2004]^Citation28)
Age of onset	33–37 years	<49 years
Symptoms	Early behavioral symptom; cognitive decline; nonfluent aphasia progress to mutism; subsequent Parkinsonism; rapid progress to death (5 years, 7 years, and 9 years of survival after onset)	Motor and speech developmental delay; 12 month- to 2-year history of substance abuse; diagnosed as encephalopathy at the of age 33 years; diagnosed as severe AD at 49 years
Autopsy	Compatible with AD	Compatible with AD

Abbreviation: AD, Alzheimer’s disease.

Table 3 Comparisons of PSEN1 mutations, which could be associated with FTD-like phenotypes

Mutation	L113P	G183V	L226F	M233L	R352ins
Disease phenotype	FTD-like dementia	Pick’s disease	EOAD and FTD-like phenotypes	FTD-like dementia	FTD, but pathogenic nature unclear
Age at onset	38–52 years	52 years	33–37 years	39 years	Unknown
Family history	Positive	Positive	Positive or de novo	Unknown, no affected family members found	Unknown
Symptoms	Personality- and behavioral changes, spatial orientation	Personality changes: apathy, overeating, or frontal disinhibition	Behavioral changes; nonfluent aphasia; cognitive decline; Parkinsonism; rapid progress to death	Behavioral changes: became detached and disengaged in daily activities, impairment in communication, overeating, became paranoid	FTD
Neuroimaging	CT: frontotemporal atrophy SPECT: hypoperfusion in the frontal lobes	Severe atrophy in the frontotemporal lobes Pick bodies and Tau-positive inclusions, without Aβ deposits	Frontal- and cortical atrophy FDG-PET: cortical hypometabolism especially in bilateral parietal regions	PET: hypoperfusion and hypometabolism in the posterior parietal areas, and in prefrontal, parietal, and temporal cortex, respectively	Ubiquitin-positive but Tau-negative form of FTD

Abbreviations: FTD, frontemporal dementia; EOAD, early onset Alzheimer’s disease; CT, computed tomography; SPECT, Single-photon emission computed tomography; FDG-PET, Single-photon emission computed tomography.

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