Table 1.

Role of lncRNAs in Alzheimer's disease.

Disease	LncRNA	Species	Function	Mechanism	Ref.
Aβ accumulation	17A	H	Increases secretion of Aβ and Aβx-42/Aβx-40 peptide ratio	Promotes synthesis of an alternative splicing isoform of GABAB R2 which impairs GABA B2 intracellular signaling	[81]
	51A	H	Disease causing; produced as an antisense transcript of intron 1 of the SORL1 gene and leads to increased Aβ formation due to defected processing of APP	Reduces synthesis of SORL1 variant by inducing a splicing shift of SORL	[82,83]
	BACE1-AS	H	Involved in production of Aβ1–42 in AD and its downregulation reduces the ability of BACE1 to cleave APP and delays the senile formation of plaques	BACE1-AS produces RNA duplexes by complementing with its protein partner HuD and mRNA BACE1 and therefore increases the stability and expression of BACE1 mRNA which helps to generates additional A1-42	[84,85,28]
	BC200 (in human)/BC1 (in mouse)	H/M	Promotes aggregation and provides protection in memory deficits and spatial learning	In human, gene expression is altered as BC200 binds with PABP1, a regulator of translation initiation, after being transported as ribonucleoprotein particles to the dendritic processes; in mouse, in association with FMRP, APP mRNA translation and aggregation of Ab in brain are induced by BC1	[86], [87], [88],49]
	NDM29	H	NDM29 is upregulated in patients with neurodegenerative diseases	Increases Aβ secretion and the Aβx-42/Aβx-40 ratio, due to increase in the synthesis of APP, induced by NDM29-dependent cell maturation	[89], [90], [91]
	LRP1-AS	H/M	Transcribed antisense to LRP1; negatively regulates the APP trafficking and Aβ processing and Aβ accumulation function of LRP1	Decreases LRP1 expression at protein and RNA levels by reducing LRP1 promoter activity induced by a transcriptional complex consisting of transcription factor Srebp1, and its interacting partner Hmgb2.	[61]
	SNHG1	H/M	Attenuation of the Aβ mediated effect by selectively targeting KREMEN1	Aβ treatment induces expression of SNHG1 while repression of it in Aβ treated cells reduces effects of Aβ on MMP and cell viability; SNHG1 mediated miR-137 sponge causes attenuation of the Aβ mediated effect by selectively targeting KREMEN1	[54], [55], [56]
Genetic polymorphism	TCONS_00021856/ linc-SLITRK5-11	H	Polymorphism in lncRNA TCONS_00021856/linc-SLITRK5-11 gene	At rs7990916 (T > C) is differentially present in Alzheimer's patients	[78]
Immune response	H19	H	Neuro-inflammation induction	HDAC1-dependent M1 microglial polarization is induced	[65]
	Lethe	M	Inflammatory signaling regulation	NF-kB subunit RelA binding with DNA is inhibited by Lethe- RelA interaction and corresponding target gene activation is halted	[66]
	lincRNA-Cox2	M	Distinct classes of immune gene expressions are either induced or inhibited	Interactions of lincRNA-Cox2 with heterogeneous nuclear; ribonucleoprotein A/B and A2/B1 is required for target gene inhibition	[42]
	NEAT1	H/M	Induces innate immune response; helps in activation of antiviral cytokine genes like IL-8	NEAT1 binds with NONO, SFPQ, PSF, Ezh2 and relocates SFPQ from IL8 promoter to the paraspeckles, that results in transcriptional activation of IL8	[66,[70], [71], [72], [73]
	MALAT1	H	Regulation of glucose mediated up-regulation of IL-6 and TNF- alpha	By activation of SAA3 expression	[74]
Neurogenesis and synaptic function	MALAT1	H/M	Synaptic density regulation	By modulating the recruitment of SRSF1,SFPQ at the transcription site	[75], [76], [77]
	antisense UchL1	M	By the regulation of UchL1, AS-UchL1 is involved in neurodegenerative diseases and brain function	Antisense Uchl1 RNA helps in overlapping Uchl1 mRNA for activation polysomes in translation purposes	[44]
	Dali	H/M	Neural differentiation regulation	DNA methylation of CpG island-associated promoters are regulated in trans by the interaction of DNMT1 DNA methyltransferase in human and mouse	[67]
	Miat	M	Neurogenic commitment	Dysregulation of Miat results in defective splicing of Wnt7b and has pleiotropic effects on brain development	[45]
	Pnky	M	Neurogenesis regulation of embryonic and postnatal neural stem cell populations	By interacting with PTBP1, the splicing regulator	[46]
	PVT1	M	Autophagic inhibition in diabetes (and diabetes associated AD) decreases PVT1 concentration	Hippocampal neurons are protected from impairment of synaptic plasticity and apoptosis by PVT1-induced autophagy, and helps in betterment of cognitive impairment in diabetes	[47]
	RMST	H	Neural stem cell fate regulation	Needed for the binding of promoter regions of neurogenic TFs to Sox2	[68]
	Evf2	M	In early dentate gyrus and postnatal hippocampus mouse mutants of Evf2 showed less GABAergic interneurons	In the Dlx5/6 intergenic region DLX and MECP2 transcription factors are recruited that controls expression of Dlx5, Dlx6 and Gad1	[48]
	GDNFOS	H	Disease causing; transcribed from the opposite strand of GDNF gene	GDNFOS negatively regulates the expression of GDNF; therefore in mature temporal gyrus of AD patients, the GDNF peptide is downregulated	[59,60]
	Sox2OT	H/M/R	Induction and/or maintenance of a TF Sox2 expression	In the cerebral cortex of the developing mouse brain, Sox2OT promotes neurogenesis and neuronal differentiation by repressing Sox2; it is also differentially expressed in early and late disease stages the AD model mouse.	[92,62,63]
	BDNF-AS	H/M	Antisense transcript to BDNF, interacts with its protein binding partner PABPC1 and negatively regulates BDNF level	Decrease in BDNF level further down regulates an immediate-early gene, involved in synaptogenesis and synaptic plasticity called ARC	[93,31]
Neurogenesis and synaptic function and neuronal apoptosis	NAT-RAD18	R	Disease causing and is upregulated in AD; transcribed from the antisense of protein coding gene Rad18	NAT-Rad18 downregulates the expression of DNA repair protein Rad18 and enhance susceptibility to neuronal apoptosis; involved in PCNA ubiquitination, DNA repair and nerve injury	[57]
	EBF3-AS	H/M	Transcribed from the opposite strand of EBF3 and is up-regulated in the hippocampus of APP/PS1 mice	EBF3-AS deficiency decreases EBF3 levels inhibits OA or Aβ induced apoptosis in human SH-SY5Y cell	[37]
rRNA transcription and methylation	LoNA	M	Regulates rRNA transcription and methylation	rRNA transcription is regulated by binding to nucleolin and decreases its activity, while methylation is regulated by interaction with fibrillarin	[42,94]