Table 1.

Post-mortem human studies examining the association between brain sphingolipids and Alzheimer’s disease

Author	Brain regions and sample size	Findings
Pettegrew et al. (2001)	Grey matter from MFG, MTG, inferior parietal lobule, occipital cortex, and cerebellar cortex: 45 AD, 11 NC.	↑ SM in AD vs. NC when all brain regions were combined or individually in cerebellum and inferior parietal cortex but not in Occipital, Superior/Middle Frontal or Superior Temporal Cortices.
		Levels of SM positively correlated with the number of AB plaques, but not with neurofibrillary tangles.
Han et al. (2002)	Grey and white matter from MFG, MTG, Inferior parietal lobe, CA1 portion of hippocampus and subiculum, entorhinalcortex, cerebellum: 5 CDR = 0, 3 CDR = 0.5, 4 CDR = 1, 6 CDR = 2, 4 CDR = 3.	↓ Sulfatide in grey and white matter of frontal, temporal and parietal lobes, and cerebellum, in CDR = 0.5–3 vs. CDR = 0. Sulfatide mass did not increase with increasing AD severity from CDR = 0.5 to CDR = 3.
		↑ Ceramide in both grey and white matter of all brain regions in CDR = 0.5 to CDR = 3 vs. CDR = 0 brains.
		Ceramide mass of CDR = 2 or 3 ↓ compared to CDR = 0.5 or 1 but still higher than CDR = 0.
		No differences in SM or galctosylceramide (GalC) mass or GalC sulfotransferase activity by disease severity.
Cutler et al. (2004)	Whole tissue from MFG and cerebellum: 7 AD, 7 NC.	↑ Ceramide C24:0 & Galactoceramide C24:0 and ↓ SM C24:0 in MFG of AD vs. NC. No differences in the cerebellum.
	Membrane raft preparations of Frontal Cortex: 2 NC, 5 mild AD,8 moderate AD, 12 severe AD.	↑ Ceramide C18:0 & C24:0 from AD vs. NC. Both ceramides ↑ with disease severity. No differences in Galactocylceramide, sulfatide or SM.
Huang et al. (2004)	Grey matter from frontotemporal areas of 10 AD and 10 NC.	↑ Acid ceramidase (AC) in AD vs. NC.
		Acid ceramidase colocalized in cell bodies of neurons with neurofibrillary tanges but not AB plaques.
Katsel et al. (2007)	Brain tissue from frontal, parietal, temporal and occipital areas; cingulate, caudate, hippocampus & putamen: 19 CDR = 0, 16 CDR = 0.5, 18 CDR = 1, 16 CDR = 2, 20 CDR = 0, 28 CDR = 4–5	Temporal and fronal cortices had greatest number of transcripts with altered expression.
		Several genes within sphingolipid pathway up- or down- regulated at specific disease stages vs. CDR = 0.
		Enzymes controlling long-chain ceramide (C22:0, C24:0) synthesis upregulated early in disease process (CDR = 0.5) and glucosylceramide downregulated.
		No alterations in gene expression for enzymes that control SM and glycosphingolipid turnover into ceramides.
He et al. (2010)	Grey matter from frontotemporal area: 9 AD, 6 NC.	↑ Membrane, not cytosolic, acid sphingomyelinase (ASM) and acid ceramidase (AC) activity in AD vs. NC.
	Divided samples into soluble (cytosolic) and membrane fractions.	No difference in neurtral sphingomyelinase (NSM) activity.
		↑ Ceramide and sphingosine and ↓ SM and sphingosine-1- phosphate (S1P) levels in soluble (cytosolic) fractions.
		Postive correlation between ASM activity and AB and phosphorylated tau protein (PHF-1).
		Negative correlation between S1P levels and AB and phosphorylated tau protein (PHF-1).
Bandaru et al. (2009)	Grey and white matter from middle frontal gyrus (MFG), middle temporal gyrus (MTG), and cerebellum. 30 AD (15 APOE E4 & 15 APOE E3) 26 NC (6 APOE E4 & 20 APOE E3).	AD vs. NC comparison: ↑ SM C16:0, C18:0, C22:0 & C24:0, Ceramide C18:0, C24:0 and steraoyl in grey matter; ↓ Ceramide C16:0, C22:0, C24:1, steraoyl and sulfatide in white matter of MFG. No differences in MTG.
		APOE E4 vs. E3: Among AD, E4 carriers had ↓ SM C22:0 and C24:0 and ↑ Ceramide C18:0, C24:1, and sulfatide in grey matter and ↑ Ceramide C22:0 in white matter of the MFG. No differences in the MTG or cerebellum by E4 status. Lipid levels in NC did not vary by APOE E4 allele status in any brain region.