| 1. |
- Bogdanovic, Nenad, et al.
(författare)
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[Alzheimer's disease - the most common cause of dementia]. : Alzheimers sjukdom – diagnostik och behandling i dag och i framtiden.
- 2020
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Ingår i: Lakartidningen. - 1652-7518. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is the most common cause of dementia. As many as 250,000 people in Sweden will have a dementia disease in 2050. The »amyloid cascade hypothesis« is a common model which explains how β-amyloid affects the function of the nerve cells. Alzheimer's disease has a long-lasting course and can present in typical and atypical forms. CSF analyses for »core AD CSF biomarkers« and synaptic proteins have been available for clinical diagnostics. PET scanning can detect either β-amyloid or tau aggregates in the brain of living humans. Current Alzheimer's disease therapy is based on two classes of cognition-enhancing drugs: acetylcholinesterase inhibitor and NMDA-receptor antagonist, which delays cognitive decline in most patients. The latest clinical development of potential therapy for Alzheimer's is active or passive immunotherapy against brain β-amyloid and tau, where several studies have shown varying but promising treatment effects. Non-pharmacological interventions in patients with AD aim to delay the loss of mental abilities, helping people to be independent in everyday life for as long as possible, and to increase their well-being and quality of life.
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| 2. |
- Bogdanovic, Nenad, et al.
(författare)
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Alzheimers sjukdom – diagnostik och behandling i dag och i framtiden
- 2020
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Ingår i: Läkartidningen. - 0023-7205. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is the most common cause of dementia. As many as 250,000 people in Sweden will have a dementia disease in 2050. The »amyloid cascade hypothesis« is a common model which explains how β-amyloid affects the function of the nerve cells. Alzheimer's disease has a long-lasting course and can present in typical and atypical forms. CSF analyses for »core AD CSF biomarkers« and synaptic proteins have been available for clinical diagnostics. PET scanning can detect either β-amyloid or tau aggregates in the brain of living humans. Current Alzheimer's disease therapy is based on two classes of cognition-enhancing drugs: acetylcholinesterase inhibitor and NMDA-receptor antagonist, which delays cognitive decline in most patients. The latest clinical development of potential therapy for Alzheimer's is active or passive immunotherapy against brain β-amyloid and tau, where several studies have shown varying but promising treatment effects. Non-pharmacological interventions in patients with AD aim to delay the loss of mental abilities, helping people to be independent in everyday life for as long as possible, and to increase their well-being and quality of life.
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| 3. |
- Gkanatsiou, Eleni, et al.
(författare)
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Characterization of monomeric and soluble aggregated A beta in Down's syndrome and Alzheimer's disease brains
- 2021
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Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 754
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Tidskriftsartikel (refereegranskat)abstract
- The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (A beta) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Our aim was to investigate the A beta peptide pattern in DS and AD brains to investigate differences in their amyloid deposition and aggregation, respectively. Cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (water soluble) and formic acid (water insoluble) fractions. Immunoprecipitation (IP) was performed using a variety of antibodies targeting different A beta species including oligomeric A beta. Mass spectrometry was then used to evaluate the presence of A beta species in the different patient groups. A large number of A beta peptides were identified including A beta 1-X, 2-X, 3-X, 4-X, 5-X, 11-X, and A beta peptides extended N terminally of the BACE1 cleavage site and ending at amino 15 in the A beta sequence APP/A beta(-X to 15), as well as peptides post-translationally modified by pyroglutamate formation. Most A beta peptides had higher abundance in AD and DS compared to controls, except the APP/A beta(-X to 15) peptides which were most abundant in DS followed by controls and AD. Furthermore, the abundancies of A?X-40 and A beta X-34 were increased in DS compared with AD. A beta 1-40, A beta 1-42, and A beta 4-42 were identified as the main constitutes of protofibrils (IP'd using mAb158) and higher relative A beta 1-42 signals were obtained compared with samples IP'd with 6E10 + 4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at amino acid 42. All A? peptides found in AD were also present in DS indicating similar pathways of A beta peptide production, degradation and accumulation, except for APP/A beta(-X to 15). Likewise, the A beta peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility that treatment with clinical benefit in sporadic AD might also be beneficial for subjects with DS.
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| 4. |
- Gkanatsiou, Eleni, et al.
(författare)
-
Characterization of monomeric and soluble aggregated Aβ in Down's syndrome and Alzheimer's disease brains.
- 2021
-
Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 754
-
Tidskriftsartikel (refereegranskat)abstract
- The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (Aβ) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Our aim was to investigate the Aβ peptide pattern in DS and AD brains to investigate differences in their amyloid deposition and aggregation, respectively. Cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (water soluble) and formic acid (water insoluble) fractions. Immunoprecipitation (IP) was performed using a variety of antibodies targeting different Aβ species including oligomeric Aβ. Mass spectrometry was then used to evaluate the presence of Aβ species in the different patient groups. A large number of Aβ peptides were identified including Aβ1-X, 2-X, 3-X, 4-X, 5-X, 11-X, and Aβ peptides extended N terminally of the BACE1 cleavage site and ending at amino 15 in the Aβ sequence APP/Aβ(-X to 15), as well as peptides post-translationally modified by pyroglutamate formation. Most Aβ peptides had higher abundance in AD and DS compared to controls, except the APP/Aβ(-X to 15) peptides which were most abundant in DS followed by controls and AD. Furthermore, the abundancies of AβX-40 and AβX-34 were increased in DS compared with AD. Aβ1-40, Aβ1-42, and Aβ4-42 were identified as the main constitutes of protofibrils (IP'd using mAb158) and higher relative Aβ1-42 signals were obtained compared with samples IP'd with 6E10+4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at amino acid 42. All Aβ peptides found in AD were also present in DS indicating similar pathways of Aβ peptide production, degradation and accumulation, except for APP/Aβ(-X to 15). Likewise, the Aβ peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility that treatment with clinical benefit in sporadic AD might also be beneficial for subjects with DS.
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| 5. |
- Johannesson, Malin, et al.
(författare)
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Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease
- 2021
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- Down syndrome (DS) is caused by trisomy of chromosome 21, which leads to a propensity to develop amyloid beta (A beta) brain pathology in early adulthood followed later by cognitive and behavioral deterioration. Characterization of the A beta pathology is important to better understand the clinical deterioration of DS individuals and to identify interventive strategies. Brain samples from people with DS and Alzheimer's disease (AD), as well as nondemented controls (NDC), were analyzed with respect to different A beta species. Immunohistochemical staining using antibodies towards A beta was also performed. Elevated levels of soluble A beta protofibrils and insoluble A beta x-40 and A beta x-42 in formic acid brain extracts, and elevated immunohistochemical staining of A beta deposits were demonstrated with the antibody BAN2401 (lecanemab) in DS and AD compared with NDC. These data and the promising data in a large phase 2 CE clinical trial with lecanemab suggest that lecanemab may have the potential to preserve cognitive capacity in DS. Lecanemab is currently in a phase 3 CE clinical trial.
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| 6. |
- Santillo, Alexander F., et al.
(författare)
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Frontotemporal demenssjukdom
- 2023. - 2
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Ingår i: Boken om demenssjukdomar. - 9789147144365 ; , s. 38-55
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Bokkapitel (populärvet., debatt m.m.)
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| 7. |
- Tofiq, avin, 1996-, et al.
(författare)
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Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer's Disease : A Randomized Controlled Trial-The OmegAD Study
- 2021
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:3, s. 1291-1301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer's disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD.OBJECTIVE: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE).METHODS: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n = 18) or placebo (n = 15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6.RESULTS: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable.CONCLUSION: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.
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