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Membrane Lipids, Selectively Diminished in Alzheimer Brains, Suggest Synapse Loss as a Primary Event in Early‐Onset Form (Type I) and Demyelination in Late‐Onset Form (Type II)

Published on Jun 28, 2008in Journal of Neurochemistry4.87
· DOI :10.1046/j.1471-4159.1994.62031039.x
Lars Svennerholm63
Estimated H-index: 63
,
Carl-Gerhard Gottfries38
Estimated H-index: 38
Cite
Abstract
: Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentration of gangliosides—a marker for axodendritic arborization—was reduced to 58–70% of the control concentration in all four gray areas (p < 0.0001) and to 81 % in frontal white matter (p < 0.01) of AD type I cases, whereas it was only significantly reduced in temporal cortex (p < 0.01), hippocampus (p < 0.05), and frontal white matter (p < 0.05) in AD type II cases. The concentration of phospholipids was also significantly reduced (p < 0.01–0.0001) in all four gray areas of AD type I cases but in no area of AD type II cases. The loss of cholesterol was only 50% of the corresponding phospholipid diminution in AD type I. These results suggested a pronounced loss of nerve endings in AD type 1. The characteristic membrane lipid disturbance in AD type II was a loss of myelin lipids. This is the first time a fundamental biochemical difference has been shown between the two major forms of AD.
  • References (45)
  • Citations (253)
Cite
References45
Newest
Published on Apr 1, 1992in Neurochemistry International3.99
Ivica Kracun8
Estimated H-index: 8
(University of Zagreb),
Svjetlana Kalanj3
Estimated H-index: 3
(University of Zagreb)
+ 1 AuthorsCedomir Cosovic8
Estimated H-index: 8
(University of Zagreb)
Abstract In Alzheimer's disease, all ganglio-series gangliosides (GM1, GD1a, GD1b and GT1b) were found to be decreased in temporal and frontal cortex, and nucleus basalis of Meynert. In addition, in Alzheimer's disease simple gangliosides (GM2, GM3) were elevated in frontal and parietal cortex, possibly correlating to accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.
Roger M. Nitsch11
Estimated H-index: 11
(Harvard University),
Jan Krzysztof Blusztajn25
Estimated H-index: 25
(Harvard University)
+ 3 AuthorsRichard J. Wurtman104
Estimated H-index: 104
(Harvard University)
Abstract To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decr...
Published on Jan 1, 1992in Neuroscience3.24
Hans Lassmann136
Estimated H-index: 136
(University of Vienna),
R. Weiler12
Estimated H-index: 12
(University of Innsbruck)
+ 6 AuthorsH. Winkler51
Estimated H-index: 51
(University of Innsbruck)
Abstract We have analysed several markers for small synaptic vesicles (synaptin-synaptophysin, p65 and SV2) and large dense-core vesicles (chromogranin A, secretogranin II/chromogranin C) in the brains of patients with Alzheimer's disease, and normal controls by immunoblotting and immunohistochemistry. In comparison to age-matched controls the levels of all three synaptic vesicle markers were decreased in temporal cortex of Alzheimer patients. On the other hand, the levels of chromogranin A were...
Published on Jan 1, 1992in Trends in Pharmacological Sciences11.52
Sam Gandy54
Estimated H-index: 54
(Rockefeller University),
Paul Greengard164
Estimated H-index: 164
(Rockefeller University)
Abstract Cerebral deposition of fibrils formed from the β/A4 amyloid protein is an invariable feature of Alzheimer's disease. Evidence suggests that generation of such fibrils may be involved in the etiology of this disease, since mutations in the coding region of the β/A4 amyloid precursor protein (APP) gene segregate with familial cerebral amyloidoses, including familial Alzheimer's disease. Transgenic models of cerebral amyloidosis have been produced, and some progress has been made in elucid...
Published on Nov 1, 1991in Brain Research2.93
Walter Schubert7
Estimated H-index: 7
(University of Bonn),
R. Prior7
Estimated H-index: 7
(Heidelberg University)
+ 4 AuthorsKonrad Beyreuther90
Estimated H-index: 90
(Heidelberg University)
Abstract We have recently shown that the amyloid βA4 precursor protein (APP) is synthesized in neurons and undergoes fast axonal transport to synaptic sites [Koo et al., Proc. Natl. Acad. Sci. U.S.A. , 87 (1990) 1561–1565]. Using immunofluorescence, laser confocal microscopy and immunoelectron microscopy with simultaneous detection of APP and synaptophysin, we now report a preferential localization of APP at synaptic sits of human and rat brain and at neuromuscular junctions. APP is further foun...
Published on Oct 1, 1991in Annals of Neurology9.50
Robert D. Terry59
Estimated H-index: 59
(UCSD: University of California, San Diego),
Eliezer Masliah139
Estimated H-index: 139
(UCSD: University of California, San Diego)
+ 5 AuthorsRobert Katzman65
Estimated H-index: 65
(UCSD: University of California, San Diego)
We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reve...
Published on Jun 1, 1991in Journal of Neurochemistry4.87
Lars Svennerholm63
Estimated H-index: 63
(University of Gothenburg),
Kerstin Boström10
Estimated H-index: 10
(University of Gothenburg)
+ 1 AuthorsBirgitta Jungbjer7
Estimated H-index: 7
(University of Gothenburg)
: The membrane lipid composition of human brain has been studied in 21 men and 18 women 60–97 years of age. This brain tissue series is unique, because it has been obtained only from individuals who lived a normal social life in their own homes and died suddenly and unexpectedly from arteriosclerotic heart disease or ruptured aortic aneurysms. They had no history of neurological or psychiatric disease. Macroscopic and microscopic examinations ruled out any signs of organic brain disorder. The pe...
Published on Apr 1, 1991in Neuron14.40
Dennis J. Selkoe161
Estimated H-index: 161
(Brigham and Women's Hospital)
The salient features of the altered biochemistry of AD brain tissue and the possible role of these changes in the pathogenesis of this complex disease are reviewed here
Published on Mar 1, 1991in International Journal of Geriatric Psychiatry3.14
Kaj Blennow118
Estimated H-index: 118
(University of Gothenburg),
Anders Wallin69
Estimated H-index: 69
(University of Gothenburg),
Carl-Gerhard Gottfries38
Estimated H-index: 38
(University of Gothenburg)
Thirty-one patients with early onset Alzheimer's disease (EAD) and 44 with late onset Alzheimer's disease (LAD) were examined with regard to symptoms reflecting disturbances in various brain regions, ie frontal, parietal and subcortical symptoms. Clinical vascular factors were recorded. The albumin ratio (CSF albumin/serum albumin) was used as a measure of the blood-brain barrier (BBB) function. Parietal symptoms were more common in EAD than in LAD, both among mildly demented patients (60% in EA...
Cited By253
Newest
Published on Dec 1, 2019in Scientific Reports4.01
Min Kyoo Shin7
Estimated H-index: 7
(SKKU: Sungkyunkwan University),
Min-Suk Choi + 3 AuthorsKil Lyong Kim17
Estimated H-index: 17
(SKKU: Sungkyunkwan University)
Brain-derived neurotrophic factor (BDNF) plays crucial roles in memory impairments including Alzheimer’s disease (AD). Previous studies have reported that tetrasialoganglioside GQ1b is involved in long-term potentiation and cognitive functions as well as BDNF expression. However, in vitro and in vivo functions of GQ1b against AD has not investigated yet. Consequently, treatment of oligomeric Aβ followed by GQ1b significantly restores Aβ1–42-induced cell death through BDNF up-regulation in primar...
Published on 2019in PLOS ONE2.78
Myungwon Choi (KU: Korea University), HyunChul Youn1
Estimated H-index: 1
(KU: Korea University)
+ 5 AuthorsCheol E. Han16
Estimated H-index: 16
(KU: Korea University)
Several metrics of analysis of magnetic resonance imaging (MRI) have been used to assess Alzheimer’s disease (AD)-related neurodegeneration. We compared four structural brain MRI analysis metrics, cortical thickness, volume, surface area, and local gyrification index (LGI), in different stages of AD-related cognitive decline. Participants with normal cognition, mild cognitive impairment, and AD were included (34 participants per group). All undertook the Consortium to Establish a Registry for Al...
Increasing numbers of individuals suffer from neurodegenerative diseases, which are characterized by progressive loss of neurons. Oxidative stress, in particular, the overproduction of Reactive Oxygen Species (ROS), play an important role in the development of these diseases, as evidenced by the detection of products of lipid, protein and DNA oxidation in vivo. Even if they participate in cell signaling and metabolism regulation, ROS are also formidable weapons against most of the biological mat...
Published on Apr 1, 2019in Molecular Neurobiology4.59
Md. Sahab Uddin8
Estimated H-index: 8
(SEU: Southeast University),
Md. Tanvir Kabir2
Estimated H-index: 2
(BRACU: BRAC University)
+ 3 AuthorsGhulam Md Ashraf15
Estimated H-index: 15
(KAU: King Abdulaziz University)
Alzheimer’s disease (AD) is an immutable neurodegenerative disease featured by the two hallmark brain pathologies that are the extracellular amyloid s (As) and intraneuronal tau protein. People carrying the APOE4 allele are at high risk of AD concerning the ones carrying the e3 allele, while the e2 allele abates risk. ApoE isoforms exert a central role in controlling the transport of brain lipid, neuronal signaling, mitochondrial function, glucose metabolism, and neuroinflammation. Regardless of...
Published on Jan 1, 2019
Liana Dehelean1
Estimated H-index: 1
,
Mirela Sarbu5
Estimated H-index: 5
+ 1 AuthorsAlina D. Zamfir23
Estimated H-index: 23
Published on Jan 1, 2019in Molecular and Cellular Neuroscience2.85
Wanda M. Snow10
Estimated H-index: 10
,
Kensuke Oikawa14
Estimated H-index: 14
+ 1 AuthorsBenedict C. Albensi20
Estimated H-index: 20
(UM: University of Manitoba)
Abstract In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid β plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mice in this model, but whether this extends to synaptic function is unknown. We investigated the influence of background strain on basal synap...
Published on Jul 1, 2018in Alzheimers & Dementia14.42
Shahzad Ahmad5
Estimated H-index: 5
(EUR: Erasmus University Rotterdam),
Christian Bannister5
Estimated H-index: 5
(Cardiff University)
+ 12 AuthorsJulie Williams60
Estimated H-index: 60
(Cardiff University)
Abstract Introduction Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways. Methods We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging...
Published on Jun 1, 2018in Biochimica et Biophysica Acta3.79
Sarah Caughlin4
Estimated H-index: 4
(UWO: University of Western Ontario),
Shikhar Maheshwari2
Estimated H-index: 2
(UWO: University of Western Ontario)
+ 6 AuthorsShawn N. Whitehead14
Estimated H-index: 14
(UWO: University of Western Ontario)
Abstract Background Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains u...
Published on Jan 1, 2018
Sandro Sonnino53
Estimated H-index: 53
(University of Milan),
Elena Chiricozzi6
Estimated H-index: 6
(University of Milan)
+ 3 AuthorsAlessandro Prinetti35
Estimated H-index: 35
(University of Milan)
Abstract Since the structure of GM1 was elucidated 55 years ago, researchers have been attracted by the sialylated glycans of gangliosides. Gangliosides head groups, protruding toward the extracellular space, significantly contribute to the cell glycocalyx; and in certain cells, such as neurons, are major determinants of the features of the cell surface. Expression of glycosyltransferases involved in the de novo biosynthesis of gangliosides is tightly regulated along cell differentiation and act...
Published on Jan 1, 2018
Robert W. Ledeen31
Estimated H-index: 31
(RU: Rutgers University),
Gusheng Wu30
Estimated H-index: 30
(RU: Rutgers University)
View next paperEvidence for a membrane defect in Alzheimer disease brain.